Bills vs. Cardinals Prediction, Odds, Pick: NFL Week 1

Seeking an extension of their strong record in Buffalo, the Bills welcome the Cardinals for Week 1 of the 2024 season. 

Questions surround the Bills, the current favorites in the AFC East odds. Buffalo lost both Stefon Diggs and Gabe Davis this offseason, leaving unknowns about their offense. 

As for Arizona, they’re projected to finish last in their division based on NFC West odds following a 4-13 campaign in 2023. 

Let’s take a look at the NFL Betting Lines for the Week 1 game, along with my prediction. 

Bills vs. Cardinals Odds

• Buffalo Bills Moneyline: -275
• Arizona Cardinals Moneyline: +220
• Game Spread: Bills -6
• Game Over/Under: 48 Points

Bills vs. Cardinals Prediction

My prediction for this game is the game total over 48 points (-110). 

The Bills offense might run into issues when they play good defenses. However, Arizona’s defense is hot garbage. 

Last season, Arizona played seven games against teams 10th or better in offensive DVOA. They allowed 31.6 points per game and allowed five of seven to clear 31 points. 

Although a majority of those contests came at home in a domed environment, this remains a Bills offense that bossed bad defenses outdoors. 

Buffalo played only three games against teams 28th or worse in defensive DVOA, but head coach Sean McDermott’s team averaged 31 points per game. 

At the same time, Arizona’s offense offers significant upside heading into 2024. 

Remember, this team put up 24 points on the Ravens sans Kyler Murray and cleared 20 points in five of Murray’s eight starts. 

Buffalo’s defense also lost some key personnel this offseason. Corner Tre’Davious White and safeties Jordan Poyer and Micah Hyde all departed. 

Plus, linebacker Matt Milano is out indefinitely for Buffalo after tearing his triceps in the preseason. 

With Murray, the Cardinals ranked ninth in EPA per play. Expect points to flow for Arizona against an average Buffalo defense.