NFL Odds for Week 4: Opening Betting Lines, Spreads & Totals - Panthers push Patriots all the way

We’re now 3 weeks into the 2025 NFL season, and to say things have been chaotic would be a gross understatement. We’ve seen some insane 4th quarters, with comebacks, touchdowns, and even blocked kicks feature in Week 3, but now it’s time to turn our attention to NFL Week 4 and the opening betting lines and odds. The team of Pickswise NFL handicappers have started the season with a 55-38-1 record, and will be looking to build on that further with their NFL predictions on the side and total for every game this the week – and throughout the rest of the season. Check out our NFL best bets page for our 5-star plays, but for now, let’s break down the NFL Week 4 opening lines and give our best early bet to make right now before the odds change.

NFL Week 4 opening lines and odds 

Odds available at bet365 at time of publishing.

• Seahawks +1 (-115) vs Cardinals -1 (-105) — Thursday Night Football
• Vikings -1.5 (-110) vs Steelers +1.5 (-110)
• Eagles -3 (-105) vs Buccaneers +3 (-115)
• Commanders -2.5 (-110) vs Falcons +2.5 (-110)
• Saints +16.5 (-110) vs Bills -16.5 (-110)
• Browns +8.5 (-110) vs Lions -8.5 (-110)
• Titans +7 (-105) vs Texans -7 (-115)
• Panthers +4.5 (-110) vs Patriots -4.5 (-110)
• Colts +3.5 (-115) vs Rams -3.5 (-105)
• Jaguars +4 (-110) vs 49ers -4 (-110)
• Bears +1 (-110) vs Raiders -1 (-110)
• Packers -6 (-115) vs Cowboys +6 (-105) — Sunday Night Football
• Jets +2.5 (-105) vs Dolphins -2.5 (-115) — Monday Night Football
• Bengals +7.5 (-110) vs Broncos -7.5 (-110) — Monday Night Football

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Best bet for NFL Week 4: Panthers +4.5 over Patriots (-110)

The Carolina Panthers picked up their first win of the season with a 30-0 demolition of the Falcons last week, and they can at least keep things close when they face the New England Patriots. Carolina is a team I was more positive about than most heading into the season, as they seemed to finally be figuring it out on the back end of the 2024 campaign, going 4-5. Most notably, Bryce Young finally looked like a competent NFL quarterback, and he looks to have taken another step forward this year. Young almost engineered an excellent comeback against the Cardinals in Week 2 and last Sunday helped orchestrate a perfect game plan against Atlanta.

As for the Patriots, they will feel hard done by to have lost to the Steelers last week despite posting nearly double the number of total yards. New England ultimately lost the game because of ball security, fumbling the pigskin 4 times in total. While this Patriots team has shown flashes of progression this year, they are still making too many mistakes and look to need more time to allow Drake Maye to progress under Mike Vrabel.

Furthermore, Carolina’s defense has allowed just 7 points across its last 6 quarters of football, indicating they can slow down this Patriots offense and take advantage of any potential miscues. The Pats do have a great shot at winning this game, but the Panthers have shown enough this year to suggest they can at least stay within a field goal.

Don’t miss our NFL Week 4 picks for every game with our experts currently boasting a 55-38-1 record for +34 units!