NFL Week 3 Opening Lines, Odds & Best Bets: 49ers showcase Super Bowl credentials at Cardinals' expense

The 2026 NFL season rolls on as we enter Week 3, and we're already beginning to separate the contenders from the pretenders. Getting things going on Thursday Night Football is a Falcons vs Packers matchup where Atlanta desperately needs to show something to avoid falling to 0-3, while the Packers will be out to build some momentum after they escaped MetLife with an overtime victory over the Jets last Sunday. We've also got Rams vs Broncos on Sunday Night Football in a potential Super Bowl preview, while Eagles vs Bears closes things out on Monday Night Football.

Make sure you check out our NFL predictions on the side and total for every NFL Week 3 game and every matchup throughout the entire season. Last season we went 311-251-4 for a profit of +90.1 units, and we're looking to stay red hot this year. Also, keep an eye on our NFL best bets for our top picks of the week. But for now, let's break down the NFL Week 3 opening lines and give our early pick to lock in right now.

NFL Week 3 Opening Lines and Odds

Odds available at Bet365 Sportsbook at time of publishing  

• Atlanta Falcons +6.5 (+100) vs Green Bay Packers -6.5 (-120) - Thursday Night Football
• Carolina Panthers -2.5 (-120) vs Cleveland Browns +2.5 (+100)
• Cincinnati Bengals -3.5 (-110) vs Pittsburgh Steelers +3.5 (-110)
• Houston Texans -2.5 (-110) vs Indianapolis Colts +2.5 (-110)
• Kansas City Chiefs -11.5 (-110) vs Miami Dolphins +11.5 (-110)
• LA Chargers +7 (-110) vs Buffalo Bills -7 (-110)
• New England Patriots +2.5 (-105) vs Jacksonville Jaguars -2.5 (-115)
• New York Jets +6.5 (-105) vs Detroit Lions -6.5 (-115)
• Seattle Seahawks -6.5 (-110) vs Washington Commanders +6.5 (-110)
• Tennessee Titans +5.5 (-105) vs New York Giants -5.5 (-115)
• Arizona Cardinals +8.5 (-110) vs San Francisco 49ers -8.5 (-110)
• Minnesota Vikings -2.5 (-110) vs Tampa Bay Buccaneers +2.5 (-110)
• Baltimore Ravens -2.5 (-125) vs Dallas Cowboys +2.5 (+105)
• Las Vegas Raiders +3.5 (-120) vs New Orleans Saints -3.5 (+100)
• LA Rams -2.5 (-110) vs Denver Broncos +2.5 (-110) - Sunday Night Football
• Philadelphia Eagles -3.5 (-115) vs Chicago Bears +3.5 (-105) - Monday Night Football

NFL Week 3 Early Best Bet: San Francisco 49ers -8.5 over Arizona Cardinals (-105)

Odds courtesy of FanDuel Sportsbook available at time of publishing

This may look like a bit of a square play, but I believe the 49ers should at least be a double-digit favorite in this spot, and can see that being the case come Sunday. So with that in mind, I'm locking in San Francisco before this number moves.

The Niners have already flashed their Super Bowl credentials by absolutely trouncing the LA Rams in Australia and then flying home to do the same to the Dolphins. While critics will be quick to say that the Rams may have beaten themselves in Melbourne with poor game preparation and that everyone is going to dominate Miami this year, but you can only beat what's in front of you, and head coach Kyle Shanahan's unit already looks like a well-oiled machine.

After a rough travel schedule, the 49ers now get to remain at home for a week and get ready for this divisional battle with the Cardinals, and Arizona may be getting too much credit for their surprise opening-week win over the Chargers. LA looks in rough shape following its loss to the Raiders, and the Cardinals looked a lot more like what people expected them to be last Sunday in their 31-7 loss to the Seahawks. Arizona managed just 151 yards of total offense as they were thoroughly dominated in all phases of the game by the Super Bowl champs, and I don't see how things get any better now they have to travel to Levi's Stadium.

The 49ers will look to keep the momentum going and continue flexing their muscles in a hot NFC West division, and unfortunately it's likely to come at Arizona's expense. I'm jumping on this now before it reaches 10 points.

Find out our NFL picks for EVERY Week 3 matchup and throughout the entire 2026 season!