NFL Odds for Week 6: Opening Betting Lines, Spreads & Totals - Buccaneers sail past 49ers
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.
Tom Coughlin gets candid on Colts’ Daniel Jones mistreatment with Giants
Former New York Giants head coach Tom Coughlin joined the Up & Adams Show to discuss Daniel Jones and his mistreatment with the Giants.
Daniel “Indiana” Jones is one of the highlights of the 2025 NFL season. His surge with the Indianapolis Colts is shocking the entire NFL community after his rollercoaster tenure with the New York Giants.
Many are talking about the sudden change of expectations for the quarterback. Jones was brought in to compete against Anthony Richardson as the starting QB and took the starting job during camp. He began the season on fire for the Colts, and the team is 4-1 on the year. The expectations are now that he should lead this team to the postseason.
Former New York Giants head coach Tom Coughlin joined the Up & Adams Show with Kay Adams to discuss Jones and his mistreatment with the Giants. Adams asked what it really comes down to.
“I’m not the only person saying it, but I'll say it for my own. I like this young man. He is a really really good young man, and you know what he went through in New York, you wouldn't want for anybody. You wouldn't want that for your son, obviously. But it's so good for all of us who are, you know, fans of this young player that he's doing well and he's having a good experience playing the game that he loves, and I've texted him and so on and so forth, which I know Eli and he are very close. I'm just so happy for him and his family. I really am.”
The Giants have been in a bad place the last few seasons, but are hoping to turn things around with Jaxson Dart now the starting QB. Jones had an injury history with the Giants, but it's looking clear that the difficulties that the team went through since Jones was drafted were not all on him. We are seeing Jones dominate with the Colts. Systems matter, and Jones may have found the perfect one for himself.
The Colts recently lost kicker Spencer Shrader for the season.
