NFL Week 5 Opening Lines, Odds & Best Bets: Colts stomp on Steelers

We move on to NFL Week 5 in the 2026 season, and the unpredictable chaos appears to be continuing. The Bills were beaten by the Patriots at home, while the Rams were once again unconvincing despite pulling off the comeback win over the Eagles. The Chiefs and Vikings moved to 4-0, although they needed narrow victories over the Raiders and Dolphins to do so. Looking ahead, we have Buccaneers vs Cowboys on Thursday Night Football, Eagles vs Jaguars in London, Ravens vs Falcons on Sunday Night Football and Bills vs Rams on Monday Night Football.

Make sure you check out our NFL predictions on the side and total for every NFL Week 5 game and every matchup throughout the whole season. Also, keep an eye on our NFL best bets for our top picks of the week, with our experts currently on a 7-1 hot streak! But for now, let's break down the NFL Week 5 opening lines and give our early pick to lock in right now.

NFL Week 5 Opening Lines and Odds

Odds available at bet365 at time of publishing  

• Tampa Bay Buccaneers +9.5 (+100) vs Dallas Cowboys -9.5 (-120) - Thursday Night Football
• Philadelphia Eagles +4.5 (-105) vs Jacksonville Jaguars -4.5 (-115) - London
• Chicago Bears -2.5 (-115) vs Green Bay Packers +2.5 (-105)
• Cincinnati Bengals -7.5 (+100) vs Miami Dolphins +7.5 (-120)
• Cleveland Browns +1.5 (-105) vs New York Jets -1.5 (-115)
• Houston Texans -6.5 (-115) vs Tennessee Titans +6.5 (-105)
• Indianapolis Colts +2.5 (-110) vs Pittsburgh Steelers -2.5 (-110)
• Las Vegas Raiders +3.5 (-110) vs New England Patriots -3.5 (-110)
• Minnesota Vikings -1.5 (-110) vs New Orleans Saints +1.5 (-110)
• New York Giants +3.5 (-115) vs Washington Commanders -3.5 (-105)
• Denver Broncos -3.5 (-105) vs LA Chargers +3.5 (-115)
• Detroit Lions -4.5 (-105) vs Arizona Cardinals +4.5 (-115)
• San Francisco 49ers +2.5 (+100) vs Seattle Seahawks -2.5 (-120)
• Baltimore Ravens -3.5 (+100) vs Atlanta Falcons +3.5 (-120) - Sunday Night Football
• Buffalo Bills +2.5 (+100) vs LA Rams -2.5 (-120) - Monday Night Football

NFL Week 5 Early Best Bet: Indianapolis Colts +2.5 over Pittsburgh Steelers (-110)

Odds courtesy of FanDuel Sportsbook available at time of publishing

I understand why the Steelers are favorites for this game. After all, they get added rest for this matchup after playing on Thursday Night Football last week, while the Colts just played in London and now have to stay on the road and play in Pittsburgh. Ultimately, that's baked into the number, but I believe oddsmakers are overcompensating for that here.

I haven't been impressed by the Steelers at all this season, and while their offense has shown some improvement since looking dreadful in their first two games, I can't feel comfortable backing this team after how they performed against the Browns. Aaron Rodgers is a shell of his former self, holding the third-worst pass completion percentage in the NFL (56.8%), and I can't see that improving much against Sauce Gardner and this Colts defense.

Indianapolis hasn't set the world alight so far this season, but they pushed the Chiefs all the way on the road before big victories over the Texans and then the Commanders in London. I'm taking them to maintain their solid form and at least come close to knocking off Pittsburgh this week.

Find out our NFL picks for EVERY Week 5 matchup and throughout the entire 2026 season!