NFL Week 6 Pick’em Pool Predictions (2025)
Week 5 saw plenty of dramatic finishes, as the Arizona Cardinals invented a new way to lose, Trevor Lawrence scored one of the weirdest game-winning touchdowns you'll ever see and the New England Patriots knocked off the undefeated Buffalo Bills.
Week 6 seems as though it will be a little less dramatic, as only six games have point spreads tighter than four points. Below, I take a look at four of the most anticipated games of the week.
Here are my top NFL Week 6 pick’em pool predictions.
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NFL Week 6 Pick’em Pool Predictions (2025)
Seattle Seahawks vs. Jacksonville Jaguars
There's a general rule that you don't pick a team traveling from the West Coast to the East Coast playing in the early window. Already this season, the Los Angeles Chargers inexplicably lost to the New York Giants in this exact same scenario. But I do worry about a letdown game from the Jaguars after their Monday Night Football win against the Chiefs.
The Jaguars have now won three consecutive games, but all have been decided by seven or fewer points. The secondary is the sixth-worst in football, allowing 250.4 yards per game. That worries me against Sam Darnold and the Seahawks' fifth-ranked passing attack.
While the Seahawks haven't been great against the pass this season, they do have the third-ranked run defense, allowing just 83 yards per game. I like the run defense to shut down the Jaguars' fifth-ranked rushing attack, as the Seahawks steal one in Jacksonville.
Pick: Seattle Seahawks
San Francisco 49ers vs. Tampa Bay Buccaneers
Two 4-1 teams coming off dramatic road victories meet on Sunday in Tampa Bay for what is clearly one of the best games of the Week 6 slate. Despite an injury to starting quarterback Brock Purdy, the 49ers lead the NFL in passing yards, as Mac Jones has led the team to 290.6 yards per game.
But the Buccaneers also have one of the league's most potent passing attacks. Baker Mayfield and rookie sensation Emeka Egbuka have connected 25 times for 445 yards and five touchdowns already. While the 49ers are only allowing 207.6 passing yards per game, Mayfield hasn't been slowed down by anyone this season, throwing for at least 289 yards in each of his last two games.
The 49ers do get the mini-bye this week, as they haven't played since Thursday. However, they're dealing with a lot of injuries and will still be without Purdy and George Kittle. While what they did against the Los Angeles Rams was impressive, that was also a rivalry game. Anything can happen in divisional games, but on Sunday, I expect the better team to win.
Pick: Tampa Bay Buccaneers
Detroit Lions vs. Kansas City Chiefs
The Lions' secondary is a mess right now. Two weeks ago, they lost D.J. Reed to injured reserve (IR), and now Terrion Arnold and Khalil Dorsey are also expected to miss at least a few games. While the Chiefs' receivers aren't too frightening at the moment, Patrick Mahomes is still the one throwing the ball, and I think he's going to carve up a depleted secondary.
Of course, the Lions are going to score plenty in this game as well. They've scored at least 34 points in four consecutive games, winning three of those contests by multiple scores. This week, they'll face a defense that allowed 31 points to the Jaguars in Week 4.
This is going to be a very high-scoring game. The Lions can absolutely win, especially with the Chiefs dealing with a short week after playing on Monday Night Football. But the Chiefs are also desperate at 2-3 and playing in front of their home crowd on Sunday Night Football. Give me Mahomes in a tight contest.
Pick: Kansas City Chiefs
Chicago Bears vs. Washington Commanders
After missing two games, Jayden Daniels returned for the Commanders in Week 5. Things started shaky, with the Commanders falling behind 10-0 early. However, the offense got going in the second quarter, as the Commanders scored 27 consecutive points to secure the win. Daniels finished with 231 passing yards and a touchdown. He also added 39 rushing yards.
The Bears have won two games in a row, and they're coming off their bye week, so they should be well-rested. Yet, while the Bears' offense has been playing pretty well, the defense has been killed on the ground. The Bears are allowing 164.5 rushing yards per game, second-most in the NFL. That's going to be a huge problem against the Commanders' top-ranked rushing attack.
Look for a huge game from Jacory Croskey-Merritt, as the Commanders travel back across the country and defeat an inferior Bears team in much less dramatic fashion than a season ago.
Pick: Washington Commanders
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Phil Wood is a featured writer at BettingPros. For more from Phil, check out his archive and follow him @Phil_Wood_Jr.