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Jacksonville Jaguars quarterback Trevor Lawrence passes the ball during the fourth quarter as we offer our NFL upset picks for Week 6.
Jacksonville Jaguars quarterback Trevor Lawrence passes the ball during the fourth quarter. Photo by Corey Perrine/Florida Times-Union

No NFL favorite was safe last week as the top two moneyline teams lost, which suggests plenty of underdogs will continue to wreak havoc in Week 6.

  • The top NFL moneyline favorite at our best NFL betting sites has lost in four of five weeks
  • There are five teams with a 3-1 or better record, while the remaining 27 teams are 3-2 or worse
  • Seven of the 14 games in Week 6 have point spreads of a field goal or lower

Our NFL upset picks, part of our Week 6 predictions, start with the London game and continue into the 1:00 p.m. ET time slot, identifying two underdogs in home games while fading a rookie quarterback.

NFL underdogs to back: Week 6

NFL odds as of Wednesday and subject to change. Track the NFL scores for the latest line movement and matchup info.

Week 6 upset predictions

NFL picks made Wednesday; odds subject to change. Our NEW NFL player prop odds tool can help you find the best odds on any market across legal sportsbooks in your area!

Jaguars (+120) ⭐⭐⭐

This Bears-Jaguars line being under a field goal is a curious one considering Chicago is hot off its longest home winning streak (eight games) since 2005-06.

In addition, Caleb Williams became the first rookie quarterback to win his first three career home starts since Brock Purdy in 2022, and the Bears are coming off their largest margin of victory (26 points) since Week 17 of the 2021 season.

However, our reason for optimism with Jacksonville is that it got the proverbial “monkey off its back” with last week’s win over the Colts, as Trevor Lawrence won his first game since Week 12 of last season (he had lost nine straight starts).

The Jaguars scored 21 or more points for the first time this season, and Lawrence is developing great chemistry with Brian Thomas Jr., as he is the only rookie with at least 45 receiving yards in all five games this season.

London games can be a great equalizer of talent, and no one is more familiar with that trip across the pond than the Jaguars.

There is a big gap between BetMGM’s +120 odds and FanDuel’s +108 moneyline odds to back the underdogs. I am taking advantage of the best value at BetMGM, where a $10 winning wager would return $12 in profits.

Best odds: | Implied probability: 45.45%

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Patriots (+265) ⭐⭐

Given the frequency at which big favorites have been knocked off this year, New England beating the second-biggest underdog of the week, Houston, would not be a big surprise.

Underdogs of six or more points are 11-8 SU and 16-2-1 ATS (88.9%) this season, including two outright wins by the Cardinals and Giants last week.

This becomes a slightly more confident play if Texans big play receiver Nico Collins is ruled out with a hamstring injury that forced him out of last week’s game. New England, amid its longest home losing streak (seven games) since 1992-93, would have ended the run if its game-winning touchdown reception last week was not overturned on replay.

And the move from Jacoby Brissett (who threw for fewer than 175 passing yards in all five games this season) to rookie Drake Maye makes Houston’s preparation for this game much tougher.

Lastly, three of Houston’s four wins this season are by four or fewer points (the most in the NFL), so it is susceptible to a road upset if the ball doesn’t bounce its way.

A winning $10 wager at FanDuel’s generous +265 odds would return a payout of $36.50.

Best odds: +265 via FanDuel | Implied probability: 27.40%

Titans (+102) ⭐⭐⭐⭐

Perhaps it was not surprising that the Colts lost to the Jaguars last week, as that was Indianapolis’ 10th consecutive road loss to Jacksonville.

However, what was alarming was that Indianapolis’ defense did not record a single sack and pressured Trevor Lawrence on just 2.9% of dropbacks, which allowed Lawrence to throw for 300-plus yards for the first time in the last 10 games.

Tennessee is rested off a bye, and it will be interesting to see if it commits to the smash-mouth style of football that was so successful in Week 4 against the Dolphins.

The Titans ran for a season-high 142 yards (more than double their previous high) and now face a Colts defense that opened the season allowing 200 or more rushing yards in consecutive games for the first time since 2017.

Indianapolis had five takeaways during a brief two-game winning streak entering last week. As long as Will Levis (or Mason Rudolph if Levis is not healthy) takes care of the football, I expect the Titans to secure the home victory.

FanDuel is the only one of our top sports betting sites offering plus-money odds on the underdogs, as all other sportsbooks are at -105 or higher.

Best odds: +102 via FanDuel | Implied probability: 49.50%

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