The dogs were barking in the NFL last week, and I’m looking for a pair of underdogs to keep the upsets coming in Week 6.
The pregame narrative: Three of the four heaviest favourites (Buffalo Bills, Arizona Cardinals, Los Angeles Rams) lost outright last week. The Philadelphia Eagles also went down as favourites, meaning no undefeated teams remain.
Check out my top Week 6 NFL upset picks, featuring a best bet on the Detroit Lions against the Kansas City Chiefs.
NFL upset picks: Week 6
Best bet: Lions moneyline (+110)
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Detroit is barely an underdog in this matchup, but it’s an underdog nonetheless. And that’s shocking to me, considering how well the group has played since Week 1.
- The Lions are averaging 40.3 points and 394.8 yards during their four-game winning streak.
- In that span, they rank first in offensive EPA per play and second in defensive EPA per play, per RBSDM.com.
Now, the squad tests its mettle against the Chiefs at Arrowhead Stadium.
Kansas City has played much better over the last three games after starting the year 0-2. But it still took a loss on Monday Night Football against the Jacksonville Jaguars, and has a suspect, if not outright bad, run defence.
The Chiefs’ defence ranks 26th in yards per rush (4.8) and 31st in EPA per rush.
Detroit loves to run the football and has two backs, Jahmyr Gibbs and David Montgomery, humming behind an elite offensive line.
I expect the Lions to win this game in the trenches and put up a gaudy amount of points yet again.
Key stat: Detroit has put up 30+ points in 10 of its last 11 games dating back to Week 14 of last season.
NFL underdog predictions
49ers moneyline (+135): San Francisco’s injury report has been lit up like a Christmas tree all season, but the team keeps finding ways to win ballgames.
Having last played on Thursday Night Football, I’m hoping the extra rest will help Kyle Shanahan’s squad get ready for a huge matchup against the 4-1 Tampa Bay Buccaneers.
Brock Purdy, Jauan Jennings and Ricky Pearsall are all questionable after missing Week 5, with the first two participating in an optional practice on Monday.
That’s something to keep an eye on as the week progresses.
On the other side, Mike Evans remains out for Tampa, with Bucky Irving also questionable after missing Sunday’s game.
San Francisco has relied heavily on Christian McCaffrey, its defence, and strong play-calling to this point. The Niners have won four straight games against the Bucs, and I expect that trend to continue.
NFL upset picks made at 1:10 p.m. ET on 10/07/2025.
Avery joined NorthStar Gaming as an intern in 2022 before stepping into a full-time role soon after. He loves betting on and analyzing golf — mainly because it’s easier than actually playing — but is a fan of all sports, from the NFL to the UFC.