Several divisional matchups highlight Week 10 despite four teams having byes -- the Bears, Broncos, Eagles and Buccaneers. Among the top divisional clashes on Sunday include Bills vs. Jets (+7.5), Panthers vs. Saints (-1.5), Jaguars vs. Titans (+9.5), Vikings vs. Packers (-3.5), Rams vs. Cardinals (+7) and Steelers vs. Bengals (-3.5) on 'Sunday Night Football.' There are a few key conference matchups as well, including Texans vs. Browns (+5), Dolphins vs. Colts (-2.5) and 49ers vs. Cowboys (+4.5). Drew Lock will start for Seattle as Sam Darnold nurses quadricep and rib injuries. Visit our Kalshi promo code review and get a $55 bonus after $25+ in trades with the Kalshi promo code CBSSPORTS55:

Week 10 also features an AFC matchup on 'Monday Night Football.' That's when the visiting and winless Los Angeles Chargers take on the Baltimore Ravens (-5.5). Newly acquired quarterback Jacoby Brissett is expected to make his Baltimore debut. He was acquired via trade from the Arizona Cardinals after injuries to Lamar Jackson and Tyler Huntley, the team's top two signal callers. Undrafted rookie Joe Fagnano, who started in Week 9, will be his backup. 

Before making any Week 10 NFL picks or NFL score predictions on those games or others, you need to see the NFL against the spread, over/under and money line predictions powered by the self-learning SportsLine AI.

Built using cutting-edge artificial intelligence and machine learning techniques by SportsLine's Data Science team, AI Predictions and AI Ratings are generated for each game. The AI predictions are determined by statistically learning from each team's historical data and then quantitatively evaluating the strength of the opponent's defense by assigning a numeric value out of 100 called a matchup score. It continuously refreshes on the most recent available data and can help you spot the biggest discrepancies in the lines at NFL betting sites, and has hit thousands of 4.5- and 5-star prop picks since the start of the 2023 season. 

For Week 10, SportsLine AI has evaluated the NFL odds and provided NFL betting picks for every game. You can only see the AI predictions for the Week 10 NFL schedule here.

Top Week 10 NFL AI picks

After analyzing every game in Week 10, SportsLine AI is projecting a 38-28 win by the Bills over the Jets. The Bills, who placed second in the AFC East a year ago, lead the division this year. The Jets, meanwhile, are 2-7 on the year and are third in the division. The Jets are on a four-game losing streak. Buffalo has won each of the last five meetings with New York, including two 20-plus wins over the Jets in 2025.

The Bills are led by quarterback Josh Allen, the 2024 NFL MVP. In a 36-10 win over Baltimore on Nov. 1, he completed 21 of 34 passes for 289 yards and two touchdowns with one interception. In 17 games last season, Allen completed 69.3% of his passes for 3,668 yards and 25 touchdowns. He was intercepted 10 times.

The Jets are guided by veteran quarterback Geno Smith. In nine games this season, he has completed 67.5% of his passes for 2,078 yards and 12 touchdowns with three interceptions and a 100.5 rating. Running back Braelon Allen has carried 120 times for 598 yards (5.0 average) and three touchdowns. He also has 19 receptions for 102 yards. 

SportsLine AI is going Over (51.5) and likes the Bills (-7.5) as the better value for ATS picks. See its other Week 10 football predictions and football picks at SportsLine.

How to make Week 10 NFL picks

In addition, SportsLine AI has generated several other A+ picks that you needed to see. You need to see the AI's NFL picks before making any Week 10 NFL bets of your own. You can only see them at SportsLine.