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NFL Week 2 odds, predictions: Picks, best bets from 10,000 computer simulations
Even those not on the West Coast could have a little more interest in making Week 2 NFL picks on either the Rams or 49ers. How those teams respond after playing in Australia last week is something that will be highly observed. Both are fortunate to have home games on the Week 2 NFL schedule, with San Fran hosting Miami on Sunday, and L.A. hosting the Giants on Monday. The Niners are 12.5-point favorites for their contest, which is the biggest NFL spread of the young season. Claim the latest Polymarket promo code CBSSPORTS to get a $50 bonus after $10 in trades:
The Week 2 NFL odds also have the Rams as heavy favorites, as they’re giving 7 points to the Giants, with Big Blue getting back-to-back primetime appointments. This pair of matchups are among the six games with a line of at least a touchdown, as the opening week clearly influenced the oddsmakers. All of the updated Week 2 NFL lines are listed below, and SportsLine’s advanced computer model has all the NFL betting advice and NFL predictions you need to make the best Week 2 NFL picks now.
The model, which simulates every NFL game 10,000 times, is up well over $7,000 for $100 players on betting sites on top-rated NFL picks since its inception. The model enters Week 2 of the 2026 NFL season on a 53-39 run on top-rated picks dating back to 2024. Anybody following its picks at NFL betting sites could have seen strong returns.
Now, it has turned its attention to the latest Week 2 NFL odds and NFL betting lines and locked in betting picks for every NFL matchup. Head here to see every pick.
Top Week 2 NFL predictions
We can tell you one of the model’s strongest Week 2 NFL picks for the best betting apps is that the Seahawks (-4.5, 41.5) cover at Arizona in a Sunday 4:25 p.m. ET kickoff. Seattle prevailed in the Kickoff Game last Wednesday, and the Seahawks are 6-1 against the spread when having a rest advantage since the start of the 2025 season. Though it’s not like the reigning champs need extra rest versus Arizona as the Seahawks have defeated the Cardinals in nine straight, going 8-1 ATS over this stretch. The Cards were impressive in upsetting the Chargers in Week 1, but the former still showed its flaws as its 111 penalty yards were the second most in Week 1. The Seahawks are forecasted to win by double digits, prevailing versus the spread well over 60% of the time in an A-rated pick. See which other teams to pick here.
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Another one of its Week 2 NFL predictions: the Buccaneers (-8.5, 40.5) cover versus the Browns as Tampa is forecasted to cover in well over 50% of simulations. Perhaps no team looked worse in Week 1 than Cleveland, as the Browns allowed 34 points to Jacksonville, saw Deshaun Watson get sacked five times, and only managed a garbage-time touchdown versus backups. The Bucs disappointed themselves in a loss at Cincy but a return home should help as Cleveland’s 4-14 ATS road mark since 2024 is the worst record in the NFL. The model also has the Over hitting well over 60% of the time. See which other teams to pick here.
How to make Week 2 NFL picks
The model has also made the call on who wins and covers in every other game on the Week 2 NFL schedule and just revealed an underdog that outright wins by a touchdown, potentially giving you a huge payday. You can only get every pick for every game at SportsLine.
So what Week 2 NFL picks can you make with confidence, and which underdog should you lock in now? Check out the latest NFL odds below, then visit SportsLine to see which teams win and cover the spread, all from a proven computer model that has returned well over $7,000, and find out.
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