Andrew Wilsher
Week 6 of the 2025 NFL season is almost upon us, and with most teams now having 5 games under their belts, it’s beginning to become clear who the contenders and pretenders are. Things get started with a Thursday Night Football matchup out of the NFC East as the Philadelphia Eagles look to bounce back from their defeat to the Denver Broncos this past Sunday with a visit to MetLife Stadium to take on the New York Giants. Other primetime games feature Lions vs Chiefs on Sunday Night Football before another Monday Night Football double-header with Bills vs Falcons and Bears vs Commanders.
Make sure you check out our NFL predictions as we add our picks on the side and total for every game throughout the week. But for now, let’s break down the NFL Week 6 opening lines and give our best early bet to make.
NFL Week 6 opening lines and odds
Odds available at DraftKings Sportsbook at time of publishing
- Eagles -7.5 (-105) vs Giants +7.5 (-115) — Thursday Night Football
- Broncos -7.5 (-105) vs Jets +7.5 (-115) — NFL London Game
- Cowboys -3.5 (-110) vs Panthers +3.5 (-110)
- Browns +4.5 (-105) vs Steelers -4.5 (-115)
- Cardinals +5.5 (-112) vs Colts -5.5 (-108)
- Chargers -5.5 (-110) vs Dolphins +5.5 (-110)
- Rams -8.5 (-105) vs Ravens +8.5 (-115)
- 49ers +3 (-108) vs Buccaneers -3 (-112)
- Seahawks -1.5 (-105) vs Jaguars +1.5 (-115)
- Titans +5.5 (-105) vs Raiders -5.5 (-115)
- Bengals +14 (-105) vs Packers -14 (-115)
- Patriots -3.5 (-110) vs Saints +3.5 (-110)
- Lions +1.5 (-115) vs Chiefs -1.5 (-105) — Sunday Night Football
- Bills -3.5 (-110) vs Falcons +3.5 (-110) — Monday Night Football
- Bears +3.5 (-110) vs Commanders -3.5 (-110) — Monday Night Football
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Best bet for NFL Week 6: Tampa Bay Buccaneers -3 over San Francisco 49ers (-105)
Odds available at FanDuel Sportsbook at time of publishing
We have a battle of 4-1 teams this Sunday but the value in this contest looks to be on the side of the Buccaneers. Tampa Bay’s lone loss this season has come at the hands of the Super Bowl champions, and Baker Mayfield and company have looked strong outside of that defeat. The Bucs earned a huge 38-35 victory over the Seahawks last week that devolved into a classic shootout. Mayfield posted 379 passing yards and 2 touchdowns, and rookie receiver Emeka Egbuka continues to go from strength to strength — going for 163 receiving yards and a score.
The Niners secured a 26-23 upset win over the Rams last week despite being 8.5-point underdogs, and while Mac Jones has proven to be more than serviceable under center (and now threatening Brock Purdy with taking his job), it remains to be seen whether he can continue this level of play at a sustained level. The extended rest will no doubt help San Fran given its laundry list of injuries, but this is still a team that is struggling to keep it all together and could be exposed when it visits Raymond James Stadium to battle a Bucs team filled with confidence.
Mayfield is playing at an MVP level at the moment, recording the fourth-most passing yards, third-most touchdowns and fewest interceptions among starters. Expect him to lead Tampa Bay to a smooth victory, and it’s worth grabbing this number now before it dips above a field goal.
Don’t miss our NFL picks for every game in Week 6! Our experts have an 86-67-1 record this season for +31 units!
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