NFL odds, lines, picks, predictions for Week 1, 2021: Top-rated model backing 49ers, Panthers

Two of the most exciting NFL quarterbacks will be on full display Sunday when Patrick Mahomes and the Kansas City Chiefs host Baker Mayfield and the Cleveland Browns. The Chiefs secured a 22-17 victory over the Browns at Arrowhead Stadium in the AFC Divisional Round last season. The latest Week 1 NFL odds from Caesars Sportsbook list Kansas City as a six-point home favorite.

There are also cross-divisional battles in Week 1 of the 2021 NFL schedule, including Seahawks vs. Colts, Chargers vs. Washington and Broncos vs. Giants. The Seahawks are 2.5-point road favorites, while the Giants are three-point home underdogs according to the Week 1 NFL spreads. All of the Week 1 NFL lines are listed below, and SportsLine’s advanced computer model has all the NFL betting advice and predictions you need to make the best Week 1 NFL picks now. 

The model, which simulates every NFL game 10,000 times, is up almost $7,900 for $100 players on top-rated NFL picks since its inception six years ago. It went a sizzling 24-14 on top-rated NFL picks last season, returning more than $800. The model also enters the 2021 season on an incredible 120-78 run on top-rated NFL picks that dates back to the 2017 season.

The model also ranked in the Top 10 on NFLPickWatch four of the past five years on straight-up NFL picks and beat more than 94 percent of CBS Sports Football Pick’em players four times during that span. Anyone who has followed it is way up.

Now, it has turned its attention to the latest Week 1 NFL odds from Caesars and locked in picks for every NFL matchup. Head here to see every pick.

Top Week 1 NFL predictions

One of the top Week 1 NFL predictions the model recommends: The 49ers (-7.5) cover the spread against the Lions. The 49ers and Lions were only separated by a game in the NFC standings a season ago, but a quick glance at their rosters makes it pretty clear that they’re much further apart than the records might indicate.

The 49ers will have Jimmy Garoppolo, Raheem Mostert, Deebo Samuel, George Kittle, Nick Bosa, Dee Ford and Jaquiski Tartt back in their Week 1 lineup after they all spent time on injured reserve last season. Meanwhile, the Lions took a step back in effort to rebuild their roster, swapping Matthew Stafford for Jared Goff.

The Lions also lost Kenny Golladay in free agency, and the model is predicting that the offense will struggle moving the football against a 49ers defense that ranked top five in the NFL in yards allowed despite all the defensive injuries. Detroit is projected to gain fewer than 325 yards, while the 49ers’ offense will put up nearly 450 yards of total offense. San Francisco covers in over 50 percent of simulations.

Another one of the top Week 1 NFL picks from the model: The Panthers (-5.5) cover as home favorites against the Jets. This is a revenge game for Panthers quarterback Sam Darnold, who spent his first three seasons with the Jets. Darnold will lead a Carolina offense that features Christian McCaffrey, D.J. Moore, Robby Anderson and Terrace Marshall.

McCaffrey became just the third player in NFL history with at least 1,000 rushing yards and 1,000 receiving yards in the same season in 2019. Carolina’s running back dealt with numerous injuries in 2020, but he’ll be eager to dominate a New York defense that gave up 387.6 yards per game last season.

SportsLine’s model is expecting McCaffrey to rack up nearly 130 all-purpose yards against the Jets. The model has also taken into account that the Panthers are 7-0 in their last seven games against opponents from the AFC East.

How to make Week 1 NFL picks 

The model has also made the call on who wins and covers in every other game on the Week 1 NFL schedule, and it’s calling for a Super Bowl contender to go down hard. You can only get every pick for every game at SportsLine.

So what NFL picks can you make with confidence? And which Super Bowl contender goes down hard? 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 almost $7,900 since its inception, and find out.

Week 1 NFL odds (via Caesars)

Thursday, Sept. 9 

Cowboys at Buccaneers (-8, 51.5)

Sunday, Sept. 12

Steelers at Bills (-6.5, 48.5)

Jets at Panthers (-5.5, 44.5)

Jaguars at Texans (+2.5, 44.5)

Cardinals at Titans (-3. 52)

Chargers at Washington (+1, 44.5)

Eagles at Falcons (-3, 48)

Seahawks at Colts (+2.5, 49.5)

Vikings at Bengals (+3, 47.5)

49ers at Lions (+7.5, 45)

Browns at Chiefs (-6, 54.5)

Dolphins at Patriots (-3, 43.5)

Broncos at Giants (+3, 42)

Packers at Saints (+4, 50)

Bears at Rams (-7.5, 46.5)

Monday, Sept. 13

Ravens at Raiders (+4.5, 50.5)