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Expert Monday Night Football betting predictions, best MNF prop bets, and odds analysis for Week 16. Free Monday Night Football picks and player props for tonight's game, including our top pick for an anytime touchdown.
Hello everybody, and welcome to Week 16's edition of Monday Night Football bets and props, where we will discuss props on George Kittle, Jonathan Taylor, and more! The NFL season is now into the holiday season, and we here at RotoBaller could not be more thrilled to bring you some of the best content in the market. We are excited to bring betting content to all those interested in every slate each week.
This weekly article will focus on the Monday night slate, and I will provide several betting angles for the scheduled games. I will typically offer at least one play on the game's total or spread, as well as at least three player or game props, including at least one anytime touchdown prop. Although this article will be published each week on Sunday evenings, you can always feel free to check out our Discord channel to see plays posted throughout the week.
This week's matchup features the San Francisco 49ers at the Indianapolis Colts at Lucas Oil Stadium in Indianapolis, IN. Each of these teams has soft spots in their defenses that we can exploit. Without further delay, let's get into tonight's picks for what should be an awesome Week 16 of Monday Night Football!
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Week 16 Monday Night Football Betting Odds
San Francisco 49ers @ Indianapolis Colts
Spread: 49ers -5.5
Total: 46.5
We have an inter-conference matchup this week between two teams heading in different directions when the 49ers travel to Indy to take on the Colts at Lucas Oil Stadium. While the 49ers have won four straight games and still have a shot at the top seed in the NFC, the Colts have now lost four straight and could be on their way out of the AFC playoff picture.
The 49ers have made their run backed by a defense allowing just under 21 points per game, which ranks 11th-best in the league. They also have a strong offense that scores nearly 25 points per game and is ranked in the top half of the league.
While the Colts have also shown a strong defense, allowing just 21.6 points per game, and a potent offense that scores 28 points per game, they recently lost starting quarterback Daniel Jones (Achilles) and have had to turn to 44-year-old Philip Rivers instead.
This move did not work out so well for the Colts' offense last week in Seattle, as they mustered just 16 points, and it could foreshadow what is to come for the rest of the season.
Week 16 Monday Night Football Betting Picks
There are a ton of angles we can look at when trying to find a pick for this game, but I think I want to focus a bit on the defenses in this matchup, with the current total set to 46.5, which is an average total when compared to the rest of the games on the board this week.
Both teams enter this matchup ranked in the top half of the league in points allowed, with the 49ers allowing 20.9 points per game and the Colts just below at 21.6. The strength of this Colts' defense has no doubt been their run defense, which ranks sixth-best in the league, allowing an average of just 95 rushing yards per game.
The 49ers have also shown a strong run defense, ranking 12th in the league by allowing an average of 106 rushing yards per game. The weakness of this San Francisco defense has been their secondary, which allows an average of over 227 passing yards per game, ranking them in the bottom half of the league.
That being said, I do not think Rivers is the type of quarterback we should worry about torching this defense. He threw for just 120 passing yards on 27 attempts last week while Jonathan Taylor racked up 25 carries. The Colts will likely use the same formula this week against a 49ers defense that is bend, don't break, against the run.
The 49ers will likely attempt to move the ball through the air against this Colts' defense, which has allowed the second-most passing yards per game this season; however, they will find it very difficult to run the ball, as mentioned earlier. While I do think San Francisco can cover the 5.5-point spread, I am going to take a look at the under 46.5 in this game.
The Pick: UNDER 46.5 (-120, DraftKings)
Week 16 Monday Night Football Player Props
George Kittle OVER 66.5 receiving yards (-114, DraftKings)
I mentioned above how the Colts struggle against the pass, and that is especially true against the tight end position. Overall, the Colts have allowed the fifth-most receiving yards to the tight end position by allowing an average of just over 66 receiving yards per game.
George Kittle has been heavily involved in this offense, especially in recent weeks. Over the previous five games, he has averaged nearly eight targets per game. He has turned those targets into an average of nearly 77 receiving yards on seven receptions per game. Additionally, he has gone over this total in all five games.
The 49ers will likely struggle to move the ball on the ground with Christian McCaffrey and will need to use the passing game more than usual. Kittle makes a ton of sense as the main target in the passing game and has a great shot to once again eclipse this total.
George Kittle is movin'
📺: #CHIvsSF on FOX
📱: https://t.co/waVpO909ge pic.twitter.com/bbC7vTn5Dz— NFL (@NFL) December 8, 2024
Jonathan Taylor OVER 20.5 receiving yards (-108, DraftKings)
I wanted to recommend Taylor over 23.5 rushing attempts, as the Colts will undoubtedly want to feed him the ball as much as possible to take the weight off of Philip Rivers' arm, but after digging in a bit, I think his receiving yards are a very viable option.
Taylor has gone over this total in six games this season and has a good shot to do it again here against the 49ers. Overall, San Francisco has allowed 503 total receiving yards to backs, which ranks in the bottom half of the league.
They have also allowed a total of nine running backs to eclipse this total in 2025. Four running backs have eclipsed this total since Week 11 as well. I think the Colts try to establish the run early, yet fail to do so against a 49ers defense that ranks inside the top half of the league in rushing yards allowed to backs, and therefore have to get creative with the short passing game.
Jonathan Taylor is on pace to finish with some historically great stats 😳 pic.twitter.com/dOpqLe6z2u
— NFL (@NFL) November 15, 2025
Week 16 Monday Night Football Anytime Touchdown Bet
Tyler Warren ANYTIME touchdown (+245, DraftKings)
There are several players like Taylor, McCaffrey, and Kittle that we could look at here, but we are always trying to find some decent plus-odds in this spot, and I think we are getting that with Warren, priced above +200.
Warren saw six targets last week with Rivers at the helm, and although none of those came in the red zone, Warren has seen 18 total red zone targets this season. He has also found the end zone five times this season, and could do it again here versus this 49ers defense.
Overall, San Francisco has allowed nine receiving touchdowns to tight ends, which ranks tied for third-worst in the league behind only the Steelers and Bengals, the latter of which has been historically bad. The 49ers have also been crushed recently by tight ends, having allowed six touchdowns to the position since Week 9.
Tyler Warren with the TD and the @Colts are rolling 👀 @FedEx pic.twitter.com/2EsyRKYK5X
— NFL (@NFL) October 19, 2025
