NFL Upset Picks Week 6: Ranking Best Moneyline Underdog Predictions

Last week was our most profitable from an NFL upset picks perspective, as we cashed in on two of the seven underdogs who won outright at +170 and +110 odds, respectively.

That marks two consecutive profitable weeks for these NFL picks.

Our NFL predictions for Week 6 back the underdogs in two of the four prime-time games and expect another ‘dog to keep its undefeated home record alive. 

🏈 NFL underdog rankings: Week 6 upset predictions

NFL upset picks for Week 6; pick confidence based on a 1-to-5 star scale.

🚨 Best NFL upset picks for Week 6

NFL upset picks based on the best NFL odds for each matchup; live odds included below each prediction.

🎯 Panthers (+164) ⭐⭐⭐

Carolina improved to 2-0 at home after a 17-point comeback against the Dolphins last week, which tied its largest comeback in franchise history.

The Panthers may have found an offensive identity they can build on for the rest of the year, as running back Rico Dowdle rushed for 206 yards, the most by any player in a game this season.

Dallas has scored 35-plus points in three games this season.

However, this is a challenging situation for the Cowboys, as they play on the road in back-to-back weeks against a team enjoying its second straight home game. And prior to Dallas’ road trip, its defense was on the field for more than 80 plays in a lengthy overtime tie against the Packers.

At some point, the injuries to CeeDee Lamb and several starters on the offensive line will catch up to them, and I expect it to come as early as this week. 

DraftKings offers the best value on the home underdog as the only one of the best sports betting sites to offer odds better than +160. A $10 winning wager at these 37.88% implied odds would net $0.90 more in profits ($16.40) than the lowest +155 odds on the market ($15.50). 

📊 Live Cowboys vs. Panthers odds

🎯 Lions (+100) ⭐⭐⭐⭐

It’s not every day you can find an underdog that is 18-3 SU in its last 21 games, 32-9 in its previous 41, and 41-12 in its last 53.

Not only is Detroit dominating its competition straight up, but it is also 51-21-1 ATS (70.8%) in the regular season since 2021, which trumps the best five-year ATS cover percentage (66.2%) of any team since 1990.

Quarterback Jared Goff has now covered the spread in 14 of his 22 outdoor games with the Lions. And Dan Campbell’s teams hardly get complacent, with a 24-6 ATS mark in the game after at least a six-point win and 21 covers in their last 26 games following a seven-point win or more.

The Lions now have the rest advantage against a Chiefs team that played on the road on Monday night in Week 5.

Plenty of the best sports betting apps give Detroit a better than 50/50 chance to pull off the upset. But the 50% implied probability through DraftKings’ (+100) returns the best value, a $10 profit on a winning $10 wager.

📊 Live Lions vs. Chiefs odds

🎯 Falcons (+176) ⭐⭐⭐

I am not declaring the sky is falling for the Bills, who are coming off their first loss of the season and first in 14 home games.

But Buffalo was undisciplined with a season-high 11 penalties and three turnovers, and Atlanta should be able to take advantage of a defense that allowed 6.0 yards per play to New England.

In the Falcons’ game before last week’s bye, quarterback Michael Penix Jr. turned in his second career 300-yard passing game, while running back Bijan Robinson had a career-high 181 scrimmage yards. 

Buffalo has been one of the league’s worst run defenses all season. It also allowed 61 yards after the catch to Stefon Diggs, his most since 2022 when Josh Allen was throwing him passes.

A $10 winning wager at FanDuel (+176) would net $17.60 in profits.

📊 Live Bills vs. Falcons odds

💰 Best NFL Week 6 underdog parlay

Our NFL player prop odds tool shows the best odds for every market across legal sportsbooks in your area.