NFL odds, lines, spreads: 2025 Week 16 picks, predictions from proven model

While there are four divisional games you can make Week 16 NFL picks on, only Buccaneers vs. Panthers (+3) takes place on Sunday. Even with the lack of fierce rivalries, there's no shortage of high-quality matchups for your NFL best bets. Amongst them are Cowboys vs. Chargers (+1.5), Broncos vs. Jaguars (+3), Steelers vs. Lions (-7) and Patriots vs. Ravens (-2.5). Then on Monday, the surging 49ers, who have won four straight, are 5.5-point road favorites over the reeling Colts, who have lost four straight, per the latest Week 16 NFL odds. 

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San Fran is one of nine road favorites you could make Week 16 NFL predictions on. The Bills (-10) are another as they visit Shedeur Sanders and Cleveland with an NFL spread you don't see very often. There's been over 20 double-digit lines this season, but just four of them have been with the road team giving points. The biggest of the Week 16 NFL spreads has the Texans as 14.5-point favorites, at home, over a Raiders team that just lost 31-0 to Philly.

Before locking in any NFL bets, make sure you see what SportsLine's advanced computer model has to say. 

The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on top-rated NFL picks since its inception. The model entered Week 15 on a 50-35 run on top-rated picks dating back to 2024. Anybody following could have seen HUGE returns!

Now, the model has evaluated the latest NFL odds, simulated every snap for Week 16 of the 2025 NFL season, and the results are in.

We can tell you one of the model's strongest Week 16 NFL picks is that the Ravens (-2.5, 48.5) cover versus New England on Sunday night. The model has Baltimore prevailing versus the spread 60% of the time. Another one of its Week 16 NFL predictions: the Chiefs (-3.5, 37.5) cover versus the Titans in well over 50% of simulations in a Sunday kickoff at 1 p.m. ET. The model also says the Under hits well over 50% of the time.

The model has also made the call on who wins and covers in every other NFL game this week and just revealed FOUR A-rated picks with the spread and total! You ABSOLUTELY NEED to see its NFL picks for every game before you make any NFL bets of your own!

So which NFL teams should you back in Week 16, and which four A-rated picks should you lock in RIGHT NOW? ... Join SportsLine now to see who wins and covers every single NFL game this week, all from the model on 50-35 roll on top-rated NFL picks!

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