Week 1 NFL picks, odds, 2022 best bets from advanced model: This five-way football parlay would pay out 25-1

Panthers quarterback Baker Mayfield will face his former team for the first time when the Carolina Panthers host the Cleveland Browns in the teams’ season opener on Sunday, Sept. 11. Drafted No. 1 overall by the Browns in 2018, Mayfield went 29-30 as a starter in Cleveland and led the Browns to the playoffs in the 2020 season. In July, Cleveland traded Mayfield to Carolina. The Panthers are favored by two points in the latest NFL odds from Caesars Sportsbook, while the over/under for total points scored is 41.5. The game is one of 16 on a loaded Week 1 NFL schedule. Other key NFL matchups include the reigning Super Bowl champion Rams hosting the Bills in the 2022 NFL Kickoff Game and the Broncos‘ Russell Wilson returning to Seattle to face his former team, the Seahawks. Before you make any Week 1 NFL picks or NFL parlays, be sure to see the NFL predictions and betting advice from SportsLine’s proven computer model.

The model, which simulates every NFL game 10,000 times, is up over $7,500 for $100 players on top-rated NFL picks since its inception. The model enters the 2022 NFL season on an incredible 138-97 run on top-rated NFL picks that dates back to the 2017 season. Amazingly, it hasn’t missed a top-rated pick since Week 15 last season. 

The model also ranked in the top 10 on NFLPickWatch four of the past six 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, the model has locked in five confident NFL best bets for Week 1. If you successfully parlay its picks, you’d be looking at a massive payout of around 25-1. You can only see the model’s Week 1 NFL picks at SportsLine. 

Top Week 1 NFL picks

After simulating every game 10,000 times, the model is high on the Indianapolis Colts to cover as eight-point road favorites against the Houston Texans. Indianapolis is coming off a 9-8 season in which the team narrowly missed out on a playoff spot. Houston has struggled the last two seasons, winning just four games in each year.

Last season, the Colts thoroughly flustered Texans quarterback Davis Mills. Over two games Mills, then a rookie, completed a combined 35-of-57 passes for 292 yards and zero touchdowns against Indianapolis. He threw two interceptions and was sacked four times. The Colts won the games by a combined 62-3. See which other NFL parlay picks to make here.

How to make Week 1 NFL parlays

The model also jumped on four other NFL matchups where it says the line is way off, including an underdog that wins outright. You can only see the model’s NFL Week 1 best bets and parlay at SportsLine. 

What are the model’s top Week 1 NFL picks? And which other NFL matchups should you target for a strong 25-1 payout? Visit SportsLine now to see the Week 1 NFL best bets from a model on a 138-97 run on its top-rated picks, and find out.