Colts vs 49ers Prediction and Preview - NFL Week 16, 2025
Last updated: Dec 23, 2025, 1:15AM | Published: Dec 16, 2025, 5:00AM
The Indianapolis Colts will sqaure off with the favoured San Francisco 49ers in NFL Week 16 action at Lucas Oil Stadium on Tuesday, commencing at 12:15pm AEDT.
This article features Stats Insider's prediction and tips for the Colts vs 49ers game, along with the latest betting odds and touchdown scorer tips.
Who Will Win?
Utilising trusted machine learning and data, Stats Insider has simulated the result of Tuesday's Indianapolis vs San Francisco NFL match-up 10,000 times.
Our independent predictive analytics model currently gives the 49ers a 64% chance of beating the Colts in Week 16 of the NFL season.
Colts vs 49ers: Odds
The latest Bet365 betting odds in Australia for Tuesday's NFL game at Lucas Oil Stadium are listed here:
- Head to Head: Colts $2.85, 49ers $1.44
- Line: Colts +4 ($1.91), 49ers -4 ($1.91)
- Total (Over/Under 46.5 Points): Over $1.91, Under $1.91
Odds are correct at the time of publication and subject to change.
Looking at the latest head-to-head odds, Bet365 currently has the Colts at $2.85 and the 49ers at $1.44.
The Colts are listed as 4-point underdogs against the 49ers, with odds of $1.91 available at Bet365.
For the favourite 49ers (-4) to cover the line, Bet365 offers odds of $1.91.
The over/under for total points scored is set at 46.5 with Bet365, which has odds of $1.91 for the over and $1.91 for the under.
According to Stats Insider's model, the Colts (+4) are predicted to cover the line 51% of the time, while the 46.5-point over/under is expected to is considered an equal 50-50 chance of hitting.
Colts vs 49ers: Best Bets
- Head to Head: Indianapolis at $2.85 with Bet365
- Line: Colts +4 at $1.91 with Bet365
- Total Points: Under 46.5 at $1.91 with Bet365
Our Colts vs 49ers best bets are based on detailed modelling and betting intelligence to help you place more informed bets with your chosen online bookie.
While the 49ers have a higher chance of winning the game, betting on the Colts to win is our recommended option due to the edge identified when comparing our data-led probabilities to the odds currently on offer.
Making use of the edges seen on Stats Insider is crucial to achieving long-term profitability.
Colts vs 49ers: Prediction
Stats Insider's predicted final score for Colts vs 49ers at Lucas Oil Stadium in Week 16 is the 49ers winning 25-21.
This prediction is based on each team's average score following 10,000 game simulations.
Stats Insider provides full betting coverage of the Indianapolis vs San Francisco game in Week 16, including data-driven predictions and free betting tips.
18+. Odds correct at time of publishing and subject to change.Colts vs 49ers: TD Scorer Tips
Who will score the first touchdown in Colts vs 49ers? The latest data is in.
According to Stats Insider, Indianapolis' Jonathan Taylor is the most likely player to score the first TD in Colts vs 49ers.
Taylor has an 18.3% chance of scoring the first TD at Lucas Oil Stadium, while the Colts RB has a 65.9% chance of scoring an anytime touchdown.
Scroll down for our complete list of first touchdown scorer and anytime touchdown scorer probabilities.
First Touchdown Scorer Tips
Colts First TD Tips
- Jonathan Taylor: 18.3% probability
- Tyler Warren: 5.6% probability
- Michael Pittman: 4.3% probability
- Josh Downs: 4.3% probability
- Alec Pierce: 3.5% probability
49ers First TD Tips
- Christian McCaffrey: 17.5% probability
- George Kittle: 9.2% probability
- Jauan Jennings: 8.3% probability
- Brian Robinson: 3.7% probability
- Brock Purdy: 3.2% probability
Anytime Touchdown Scorer Tips
Colts Anytime TD Tips
- Jonathan Taylor: 65.9% probability
- Tyler Warren: 27.9% probability
- Michael Pittman: 22.3% probability
- Josh Downs: 22.1% probability
- Alec Pierce: 18.5% probability
49ers Anytime TD Tips
- Christian McCaffrey: 63.0% probability
- George Kittle: 40.5% probability
- Jauan Jennings: 37.7% probability
- Brian Robinson: 19.1% probability
- Brock Purdy: 16.6% probability
Colts-49ers Projected Player Stats
Of the starting quarterbacks, the Colts' Philip Rivers is projected for 182 passing yards. The 49ers' Brock Purdy is expected to throw for 249 yards.
Colts Starting QB
- Philip Rivers: 182 projected passing yards
49ers Starting QB
- Brock Purdy: 249 projected passing yards
Colts Rushing Yards
- Jonathan Taylor: 105 projected yards
- Ameer Abdullah: 14 projected yards
- Tyler Goodson: 4 projected yards
49ers Rushing Yards
- Christian McCaffrey: 66 projected yards
- Brian Robinson: 24 projected yards
- Brock Purdy: 16 projected yards
Colts Receiving Yards
- Tyler Warren: 40 projected yards
- Michael Pittman: 39 projected yards
- Josh Downs: 33 projected yards
- Alec Pierce: 27 projected yards
- Jonathan Taylor: 22 projected yards
49ers Receiving Yards
- George Kittle: 66 projected yards
- Jauan Jennings: 60 projected yards
- Christian McCaffrey: 42 projected yards
- Kendrick Bourne: 31 projected yards
- Demarcus Robinson: 24 projected yards
Our model updates frequently, so refresh this article for the latest betting predictions before the Indianapolis vs San Francisco match-up.
As always, see Stats Insider's Best Bets for betting tips for every NFL game, as well as predictions for a wide range of other sports.
Colts vs 49ers: Week 16 Essential Details
The NFL Week 16 game between the Colts and 49ers at Lucas Oil Stadium is scheduled to start at 12:15pm AEDT on Tuesday.
- Teams: Indianapolis Colts vs San Francisco 49ers
- Date: Tuesday 23 December 2025
- Time: 12:15pm AEDT
- Venue: Lucas Oil Stadium
All dates and times mentioned in this article are in Australian Eastern Daylight Time (AEDT), unless otherwise stated.
Conclusion
Our Indianapolis vs San Francisco predictions have been made after running 10,000 data-driven simulations of the game, carefully curated by our team of skilled data scientists and analysts. We use the latest in predictive analytics technology and machine learning to ensure our NFL tips are trustworthy and reliable, giving you the knowledge you need to make informed decisions with confidence.
If you decide to use our predictions for betting purposes, it's important that you gamble responsibly and keep track of your money. For free and confidential support, call 1800 858 858 or visit gamblinghelponline.org.au.
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