NFL Week 1 Upset Picks (Rams Win on Opening Night, Giants and Jaguars Among Top Predictions)

Los Angeles Rams head coach Sean McVay.
Los Angeles Rams head coach Sean McVay. / Joe Nicholson-USA TODAY Sports
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NFL Football is back, and the BetSided team can’t wait to share our upset picks with you in each week of the 2022 season. 

There are nine different home underdogs on this week’s slate, and one of our editors is targeting a home underdog as his pick to pull off the upset. 

Using the odds at FanDuel Sportsbook, let’s break down the best underdogs for Week 1 to help you cash in on some plus money and get this season started the right way: 

Best NFL Upset Picks for Week 1 of 2022 Season

New York Giants (+215) at Tennessee Titans

This bet is more of a fade of the Tennessee Titans than a bet on the New York Giants. 

Giving up A.J. Brown in the off season, means that the Tennessee offense relies even more on Derrick Henry than it did last year. That, to me, is a big red flag. Henry struggled with injuries last season, and when he did play, he averaged only 4.3 yards per carry. 

That's 1.1 yards fewer than the previous season. For a team that finished 19th in net yards per play last season, they're looking even worse in 2022, especially considering they lost their best defensive player this year to injury in Harold Landry.

The Giants may not be a playoff team just quite yet, but a revamped offensive line and Brian Daboll leading the charge as the new head coach, I think they can get the opening week win against Tennessee. – Iain MacMillan

Jacksonville Jaguars (+120) at Washington Commanders

I’ve been screaming all summer long that the Jacksonville Jaguars are going to be much improved, and I’m ready for them to prove me right. This is a talented, young team with a fresh start that plays a turnover-prone Carson Wentz and a disappointing Washington Commanders defense. Trevor Lawrence is going to look comfortable in the pocket under Doug Pederson’s new scheme and the rest of the team will look better for it.

I don’t trust Wentz without a dominant offensive line and the best running back in the league. The Jaguars can sit back and wait for him to lose the game all by himself. – Donnavan Smoot

Los Angeles Rams (+110) vs. Buffalo Bills

There is always the fear of a Super Bowl hangover, but I don’t expect that from a team led by Sean McVay, especially against such a tough opponent. 

The Bills upgraded with Von Miller joining the team’s pass rush, but the loss of White could be huge in this game, as it could thrust rookie Kaiir Elam into a bigger role against Kupp and company. 

Remember, the last time we saw this Bills defense, it let the Kansas City Chiefs march into field goal range in just 13 seconds, eventually costing Buffalo a trip to the AFC title game. 

McVay has been fantastic to start seasons, and now he has one of the best rosters during his time in Los Angeles. I really am surprised that oddsmakers are so high on the Bills that Los Angeles is a dog in this game. Also, don’t forget that defending Super Bowl Champions are 10-5-1 ATS in their weekday season opener over the last 16 seasons. 

I think the Rams actually can win this game straight up, especially if they can feed off the momentum from the per-game ring ceremony. – Peter Dewey

Steelers +230 at Bengals

The Super Bowl hangover tour for the Cincinnati Bengals starts bright and early this year, when they take the projected last-place finisher in the division Pittsburgh Steelers a bit too lightly in Game 1 at home.

Pittsburgh has plenty of flaws, and ultimately as the season goes on, we'll start to see more and more rear their ugly head. In a game with everyone fairly healthy (assuming Diontae Johnson plays), this line is far too large in favor of a team most bettors remember shocking the Kansas City Chiefs en route to the Super Bowl a season ago before losing to the L.A. Rams.

Mike Tomlin is a wizard in these spots over the course of his career, going 45–23–2 ATS in his career as an underdog, and 29-19-1 ATS on the road. The Steelers will be in this game, and will likely need a late stand or two from their defense to hold off an explosive Bengals offense late in the matchup.

Via Brandon Anderson of TAN, division underdogs are 61–41–2 ATS (60%) in Week 1 since 2005, and 29–9–1 (76%) in the past eight seasons. Expect those numbers to go up by one in the win column, including for straight up winners on Sunday. - Ben Heisler