College Football Picks Against the Spread: Expert Betting Predictions for Week 5 (2025)

Mike's Week 5 college football betting picks against the spread for Saturday, September 27, 2025. Free CFB betting predictions, odds analysis & ATS picks from RotoBaller.

I had one of my worst weeks ever last week, hitting just 13 out of 50 picks. You have to have humility to do something like this, and sometimes these things happen. This week will be better. The worst thing I could do would be to try to make it all back this week. On the season, I'm not too far down.

We have 58 total games today, which is a little lighter than a typical Saturday. Some of that is due to fewer FBS teams playing FCS teams. You know I won't pick those. I hate huge lines anyway.

If you'd like me to advise on one of those FBS vs. FCS matchups, you can reach out on X or in the RotoBaller Discord, and I'll be happy to answer. Let's get to the picks we really care about. There are 47 FBS vs. FBS tilts today!

CFB Betting Picks for Week 5 - (9/27/25)

I will pick every college football game every week. Not a top five. Not a top 10. All of them. Big deal, right? Lots of people make picks. Well, I do them all against the spread. I take the odds of each game and average them out at all the Vegas casinos and round to the nearest half. There will be no ties here. Ties are for the other (European) football.

I think you should know who you're listening to. I've been doing this since 2014, and I have most of my record available for viewing here. This can help you determine which teams I usually pick correctly or incorrectly, as the case may be. The sheet is still under construction since I am having issues finding the articles from 2019 and 2020.

(16) Georgia Tech (-13.5) at Wake Forest

Betting Pick Confidence Factor: 2

Somehow, the Deacons have managed to hang around with a better-than-advertised Kennesaw State team and North Carolina State. I don't trust this line. This line is down 3.5 points already, and I get it. Georgia Tech didn't look great against Temple. I think Tech shows up here.

Pick: Georgia Tech -13.5

(21) USC (-6.5) at (23) Illinois

Betting Pick Confidence Factor: 2

This line is up, but I think it might be an over-adjustment. Illinois looked really bad against Indiana, but I also think that Indiana is a more complete team than USC. The USC offense is better. Can a physical Illinois defense knock them off balance?

We know that Illinois will be able to move the ball on USC. Purdue and Michigan State both did. I still like USC for under a touchdown.

Pick: USC -6.5

(22) Notre Dame (-4.5) at Arkansas

Betting Pick Confidence Factor: 2

𝐑𝐞𝐭𝐮𝐫𝐧 𝐨𝐟 𝐭𝐡𝐞 𝐊𝐢𝐧𝐠

Former Notre Dame and Arkansas Head Coach Lou Holtz will be in attendance for Saturday’s matchup in Fayetteville. The game marks the first time the programs will ever meet, having had no prior matchups in their history.

Holtz is one of the… pic.twitter.com/xmWTPp0GMG

— The Irish Tribune (@TheIrishTribune) September 24, 2025

This line has bottomed out. It opened with the Irish favored by 12.5. Let's call this the Lou Holtz Bowl. These teams have never met before, which is a little bit strange. It also explains the buzz surrounding it in Fayetteville.

I expect a high-scoring game, but the over/under is set fairly as well. This feels like the kind of game Arkansas wins. Taylen Green is going to be a problem for the Irish.

Pick: Arkansas +4.5

Rutgers at Minnesota (-5.5)

Betting Pick Confidence Factor: 2

Minnesota has burned me a lot this year. They remind me a lot of Virginia. Do they have the talent to win this by six? Absolutely. Will they? I doubt it. Rutgers feels like a safer pick.

Pick: Rutgers +5.5

Duke (-5.5) at Syracuse

Betting Pick Confidence Factor: 3

The news that Steve Angeli is out for the season is a big blow for Syracuse. The thing is, Fran Brown just plugged and played Angeli, and his stats were up there with Kyle McCord's from 2024. This offense is a quarterback's dream.

There are going to be some growing pains with Rickie Collins. The LSU transfer is going to be good in this offense, but maybe not in the first game.

Pick: Duke -5.5

Louisville (-4.5) at Pittsburgh

Betting Pick Confidence Factor: 2

This is another tough one. Pitt got torn apart on the ground by the West Virginia ground game, and Louisville is even better. Did the Backyard Brawl wake up Pitt, or make them worse? I think it may be the latter.

The status of Isaac Brown is up in the air, but his absence from most of the game against Bowling Green is likely just resting him up. I would guess that Brown plays, and we get this great showdown between Brown and Desmond Reid.

Pick: Louisville -4.5

Cincinnati at Kansas (-4.5)

Betting Pick Confidence Factor: 4

This is too low. Jalon Daniels is back. Kansas still has new stadium vibes. The Jayhawks may not lose a game at home this year. Kansas has outscored opponents 118-24 at home in three games this year.

Pick: Kansas -4.5

Central Florida at Kansas State (-6.5)

Betting Pick Confidence Factor: 2

This line is a bit shocking to me. I figured an overreaction was coming, but from the other side, after UCF handled North Carolina. K-State is 0-4 against the spread this year. Dylan Edwards is expected to be healthy for this game, but every Wildcat game this year has been decided by less than six points.

I think Kansas State wins, but all four games have been ugly for the Wildcats this year, win or lose. If I place a bet on this, it will be the money line. I'll give the juice for the win. Against the spread...it's hard to trust K-State right now.

Pick: Central Florida +6.5

South Alabama at North Texas (-12.5)

Betting Pick Confidence Factor: 3

The line is rising, and I'm not a bit surprised. South Alabama is a different team on the road, and not in a good way.

Pick: North Texas -12.5

Bowling Green at Ohio (-8.5)

Betting Pick Confidence Factor: 3

This line has been back and forth between 7.5 and 10...and everywhere in between. I still like it for anything under 10.

Pick: Ohio -8.5

Utah State at (18) Vanderbilt (-22.5)

Betting Pick Confidence Factor: 2

I understand this line. I really do. Vandy hung 70 on the Georgia State team that embarrassed them last year. I feel like Bryson Barnes is going to be a bit of a problem for Vanderbilt. This feels a bit high.

Pick: Utah State +22.5

Eastern Michigan at Central Michigan (-6.5)

Betting Pick Confidence Factor: 1

There is nothing I like about this line, but I can't deny that Eastern Michigan has looked like the better team. I would like it a lot more if it were still a point higher.

Pick: Eastern Michigan +6.5

Georgia Southern at James Madison (-17.5)

Betting Pick Confidence Factor: 2

Alonza Barnett III is the full-time starter for the Dukes now. This should have happened weeks ago.

Pick: James Madison -17.5

Arkansas State at Louisiana-Monroe (-1.5)

Betting Pick Confidence Factor: 1

Don't look now, but the Warhawks have another strong back who is going to make some Power 4 team very happy next year. Braylon McReynolds isn't as good as Ahmad Hardy, but he runs tough. I have questions about the Monroe defense, but I can't trust the Red Wolves right now.

Pick: Louisiana-Monroe -1.5

(1) Ohio State (-7.5) at Washington

Betting Pick Confidence Factor: 5

Ohio State @ Washington #Betting #OhioStateFootball #Washington

This is not a good sign, Buckeye Fans. 🤮

Money coming in on the #Buckeyes and the line keeps dropping. pic.twitter.com/G35XOpUTlo

— DHenny (@Hennything1556) September 24, 2025

That graphic is freaking terrifying. I get that Washington's home win streak is the second-longest in the country. I have watched every game from both teams. Ohio State doesn't just look a little bit better. They look a LOT better.

When the line keeps dropping despite 97% riding on the team that's dropping, the first instinct is to run. Those casinos weren't built on hunches. It was built on Vegas being right far more often than they are wrong.

Ohio State is 17-0 straight up in true road games against unranked opponents under Ryan Day. However, this is the first time the Buckeyes will be favored by less than 14 points in any of them...

— Chris Fallica (@chrisfallica) September 25, 2025

The part that I don't get is...Washington hasn't been tested. They were tied with Colorado State at the end of three quarters, and Washington State was only down a touchdown going into the fourth. This Ohio State team can close. They held off a Texas flurry after 55 minutes of dormancy.

Pick: Ohio State -7.5

(4) LSU at (13) Mississippi (-1.5)

Betting Pick Confidence Factor: 3

Every predictive metric is heavy on Mississippi. Trinidad Chambliss has changed this offense. LSU's defense made both DJ Lagway and Cade Klubnik look bad. Can Mississippi run the ball well enough to soften up the defense?

The difference is that I don't think Chambliss will make the same mistakes that Lagway did. He may not have FBS experience, but he did win a Division II national title. The Mississippi receivers are better than Clemson's or Florida's. The Ole Miss defense has had issues with mobile quarterbacks, but that's not Garrett Nussmeier.

Pick: Mississippi -1.5

Auburn at (9) Texas A&M (-6.5)

Betting Pick Confidence Factor: 4

Auburn has lost nine straight and 14 of its last 15 road games against ranked opponents (0-5 under Hugh Freeze)...

— Chris Fallica (@chrisfallica) September 25, 2025

You know, I could be snarky and say that Auburn lost to a one-handed quarterback, but that's not entirely true. The Auburn defense is going to give the Aggies' offense issues. Still, A&M at home for less than a touchdown feels safe. Auburn is still in their heads about the (completely legal) Sategna play.

Pick: Texas A&M -6.5

(11) Indiana (-7.5) at Iowa

Betting Pick Confidence Factor: 5

The more insane stat here is that Iowa has hosted just ONE team that finished better than 6-6 in the regular season since that Michigan game in 2022. Home slate last 1,092 days:
—1 team with winning record (10-2 ISU)
—5 teams that finished 6-6
—11 teams with losing record or FCS https://t.co/C0eTEHP3KH

— Alex Gookin (@_AlexGookin) September 25, 2025

Indiana punished an Illinois team that is just like Iowa, except the Illini have a better offense. Indiana isn't going to fold now.

Pick: Indiana -7.5

UCLA at Northwestern (-6.5)

Betting Pick Confidence Factor: 1

This is going to be such a horrible game. The best part about it will be the stadium.

Pick: Northwestern -6.5

California at Boston College (-6.5)

Betting Pick Confidence Factor: 4

Cal just got mopped by San Diego State. I find it hard to believe that Cal looks that bad again, but they would need to play the best game of the season after their worst. That's a lot to ask behind a freshman quarterback.

Pick: Boston College -6.5

Baylor (-20.5) at Oklahoma State

Betting Pick Confidence Factor: 2

Largest point spread for an OSU opponent coming to Stilllwater in the history of the program https://t.co/hnZG6GuheS

— 𝙋𝙞𝙨𝙩𝙤𝙡 𝙍𝙞𝙘𝙠 (@PistolRick) September 22, 2025

Mike Gundy went and addressed the team the day after he was fired. I think that lights a fire under them, especially at home. The line feels too high.

Pick: Oklahoma State +20.5

Utah (-12.5) at West Virginia

Betting Pick Confidence Factor: 2

Utah is the more talented team, but that doesn't always matter in Morgantown. I do believe in the Utah defense, so I'll just lower the wager.

Pick: Utah -12.5

Connecticut (-3.5) at Buffalo

Betting Pick Confidence Factor: 3

UConn needed a miracle to beat Delaware and had to hang on for dear life against Ball State. Ball. Freaking. State. I know that Buffalo has looked bad, but not this bad.

Pick: Buffalo +3.5

San Diego State (-2.5) at Northern Illinois

Betting Pick Confidence Factor: 1

That Cal win was kind of impressive. Impressive enough that I'm leaving this one alone.

Pick: San Diego State -2.5

Rice at Navy (-14.5)

Betting Pick Confidence Factor: 1

Ugh...I don't like that half at all.

Pick: Navy -14.5

Akron at Toledo (-20.5)

Betting Pick Confidence Factor: 1

The last thing I want to do is overreact to Toledo losing outright to Central Michigan. Picking Akron would feel like an overreaction, but I wouldn't bet this with your money.

Pick: Toledo -20.5

New Mexico State at New Mexico (-13.5)

Betting Pick Confidence Factor: 2

1st time since 1992 when both were 1-0, that New Mexico and New Mexico State will play with both possessing a winning record. First time since 1964 its happened when they have played more than one game in the season (UNM was 3-2, New Mexico State was 3-2)...

— Chris Fallica (@chrisfallica) September 25, 2025

The Rio Grande Rivalry has only been decided by more than two touchdowns once since 2013. This feels high. This rivalry is a big deal in New Mexico. Both teams play like it.

Pick: New Mexico State +13.5

Tulane (-15.5) at Tulsa

Betting Pick Confidence Factor: 2

I don't like this line at all, and you know how I feel about revolving quarterbacks. I have to go with Tulsa at home. They're not going to win outright, but...say they lose 34-21 or so.

Pick: Tulsa +15.5

Hawaii at Air Force (-6.5)

Betting Pick Confidence Factor: 3

Hawaii usually struggles on the mainland, and they can't handle an option offense.

Pick: Air Force -6.5

(15) Tennessee (-7.5) at Mississippi State

Betting Pick Confidence Factor: 4

Will the Bulldogs be able to throw on Tennessee? Yes. Will those cowbells be annoying? Yes. Is Joey Aguilar the best Tennessee quarterback since Peyton Manning? Maybe. I have a feeling that the Bulldogs get exposed here.

Pick: Tennessee -7.5

Middle Tennessee State at Kennesaw State (-7.5)

Betting Pick Confidence Factor: 3

It has been a swift fall for the Blue Raiders. Kennesaw has been a tough team this year. I don't like the half, but I do like the team trying to cover it.

Pick: Kennesaw State -7.5

Liberty at Old Dominion (-16.5)

Betting Pick Confidence Factor: 2

Wow, this is a lot. The Monarchs beat the Hokies by more than this on the road, so they should be able to cover at home.

Pick: Old Dominion -16.5

Arizona at (14) Iowa State (-6.5)

Betting Pick Confidence Factor: 3

Arizona is much better than last year, but they still aren't winning a night game at Jack Trice Stadium.

Pick: Iowa State (-6.5)

Virginia Tech at North Carolina State (-10.5)

Betting Pick Confidence Factor: 2

We learned nothing at all from Tech walloping Wofford. The team looked better, but it was a really bad team. This line is up 2.5 from the open. I feel like it's at least a half-point too high.

Pick: Virginia Tech +10.5

Jacksonville State at Southern Mississippi (-3.5)

Betting Pick Confidence Factor: 2

Both teams have looked pretty good so far, but I have to go with the Eagles at home. The people in Hattiesburg have suffered enough in the past few years.

Pick: Southern Mississippi -3.5

Western Kentucky (-4.5) at Missouri State

Betting Pick Confidence Factor: 3

The first FBS game in Springfield didn't disappoint. Maverick McIvor has struggled lately, but the Hilltoppers have still found ways to score. The Bears aren't there yet.

Pick: Western Kentucky -4.5

Memphis (-13.5) at Florida Atlantic

Betting Pick Confidence Factor: 3

This Memphis offense might have the best backfield outside of a Power 4 team. Brendon Lewis is just a running back who throws for 200 yards per game. FIU scored four rushing touchdowns on the Owls and had nearly 300 yards on the ground. This Memphis offense will do that and more.

Pick: Memphis -13.5

(6) Oregon at (3) Penn State (-3.5)

Betting Pick Confidence Factor: 3

Penn State is 4-20 v Top 10 opponents under James Franklin. One of the wins came against G5 Boise State last year in the CFP...

— Chris Fallica (@chrisfallica) September 25, 2025

We all know the numbers, and you all know how I feel about it. If the above isn't enough, check this out.

In nine career starts vs Ranked P4 opponents, Allar is 3-6, completing 54.1 pct of his passes with 11 TD, 5 INT and averaging 165.7 YPG...

— Chris Fallica (@chrisfallica) September 25, 2025

Everything points to Penn State losing the game.

Pick: Oregon +3.5

(17) Alabama at (5) Georgia (-2.5)

Betting Pick Confidence Factor: 2

The Georgia Bulldogs have only beaten Alabama inside Sanford Stadium once in the last 30 years#TNRStatOfTheDay pic.twitter.com/SP3Zjyq82G

— The Next Round (@NextRoundLive) September 25, 2025

Georgia's only win against Alabama in the last 10 meetings was the 2021 National Championship game. Alabama has Georgia's number, and Ty Simpson seems to have figured something out since the loss to Florida State.

As an underdog, Kalen Deboer’s teams have won eight of 11 games outright and covered nine of 11. As a Power 5 head coach, those marks improve to six outright wins in seven tries...

— Chris Fallica (@chrisfallica) September 25, 2025

I'm going to enjoy this game, but I'm probably not going to bet on it. This really could go either way.

Pick: Alabama +2.5

Massachusetts at (20) Missouri (-44.5)

Betting Pick Confidence Factor: 2

Missouri will run 50 times and cover.

Pick: Missouri -44.5

Washington State at Colorado State (-5.5)

Betting Pick Confidence Factor: 2

I was expecting this line, but it doesn't mean I was ready to see it. I guess the end of the Brayden Fowler-Nicolosi era in Fort Collins is approved by Vegas. After watching the Washington State "defense," I believe it.

Pick: Colorado State -5.5

San Jose State at Stanford (-2.5)

Betting Pick Confidence Factor: 1

Things have been awfully quiet in the Bay Area since the Spartans lost to Central Michigan. Stanford has looked like a good team at times. At others, they look like a high school squad. I don't trust either team. I guess that means I'm taking the home team.

Pick: Stanford -2.5

Appalachian State at Boise State (-16.5)

Betting Pick Confidence Factor: 2

Wow, this is a tough one. Boise was obliterated by South Florida. Southern Miss took out the Mountaineers. These were supposed to be two of the best Group of 5 teams. I can't trust the Boise defense to keep App State contained enough to cover this.

Pick: Appalachian State +16.5

Kentucky at South Carolina (-5.5)

Betting Pick Confidence Factor: 5

I don't think South Carolina is that far down. I think Missouri is just better than most people think.

Pick: South Carolina -5.5

Marshall at Louisiana (-1.5)

Betting Pick Confidence Factor: 1

There is a ton of fluctuation in this line. As of this writing, there are still three points worth of play in the line. The Cajuns are 1.5-point dogs at ESPN and DraftKings. They're favorites by the same amount at Bally.

If Vegas doesn't know what to do with this line, how the hell should I know? That Louisiana loss to Rice was worse than Marshall's loss to Missouri State.

Pick: Marshall +1.5

Louisiana Tech (-4.5) at UTEP

Betting Pick Confidence Factor: 2

The Bulldogs have to be the favorites in Conference USA right now. Malachi Nelson is going to throw the ball all over El Paso, but that defense can't stop anyone.

Pick: Louisiana Tech -4.5

(25) BYU (-6.5) at Colorado

Betting Pick Confidence Factor: 4

Sometimes, Colorado looks like a respectable team. Sometimes, they look like a team that got pushed around by Houston. The bad news is that BYU is more physical than Houston.

Pick: BYU -6.5

Last week's disaster was bound to make me a little skittish. I have more two-pointers than normal, with 21 out of the 51 picks. I had eight minimum bets, which is also a season high. I went with three max bets. I was lighter on the three-pointers with 13 of them. I have six four-point bets.

Good luck out there! This is a big weekend! It's time for redemption!

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