NFL Week 2 Predictions 2022: Upset Picks, Best Odds For Straight Up Winners

There were only three upsets on the first Sunday of the 2022 NFL season, but that number could increase in Week 2. A few underdogs have a better chance to beat their divisional rivals straight up than the early betting odds indicate.

Here are the best upset picks and their odds for Week 2.

New Orleans Saints (+135) vs. Tampa Bay Buccaneers [DraftKings Sportsbook]

No team has consistently given Tom Brady and the Buccaneers more trouble than the Saints. Tampa Bay is 0-4 against New Orleans in the regular season with Brady under center. Brady threw multiple interceptions in each of those first three games. In the last contest, the Bucs were shut out and Brady was sacked four times.

Tampa Bay's offense looked far from crisp in the season opener, scoring just 19 points in Dallas. Buccaneers receiver Chris Godwin suffered a hamstring injury in the contest and is expected to miss multiple weeks. Saints receivers Michael Thomas and Jarvis Landry combined for 12 receptions, 171 yards and two touchdowns in Week 1, suggesting that the veterans could be in for bounce-back campaigns.

Seattle Seahawks (+315) at San Francisco 49ers [FanDuel Sportsbook]

There are major questions about San Francisco's offense with Trey Lance under center. In the season opener, Lance looked every bit like a quarterback who has only started three games since the conclusion of the 2019 college football season. The 49ers are -400 favorites after Lance completed fewer than half of his passes against a Bears' team that's projected to be one of the NFL's worst.

The Seahawks are likely to come up short in San Francisco, but they could be a worthwhile upset pick at longer than 3/1 odds to win straight up. On their way to a last-place finish last year, the Seahawks defeated the 49ers twice. Geno Smith had a 103.0 passer rating in his limited time as Russell Wilson's replacement a season ago.

Jacksonville Jaguars (+180) vs. Indianapolis Colts [FanDuel Sportsbook]

The Colts were lucky to survive a Week 1 scare in Houston. Indianapolis came back from a 20-3 deficit in the fourth quarter, only to end in a tie the team with the league's worst Super Bowl odds. The Colts should be able to get their first win of the season against the Jaguars, but the odds for this AFC South matchup are giving Indianapolis far too much credit.

The Jaguars have a six-game winning streak against the Colts in Jacksonville. That stretch includes the last two seasons when the Jaguars won four total games. Jacksonville is likely to be improved this year, now that Trevor Lawrence is in his second season and the Jaguars have upgraded their head coach. Matt Ryan didn't look particularly sharp in his first game as a 37-year-old quarterback.