The new-look Buffalo Bills are a team to watch on Sunday as they kick off the NFL season against the retooling but dangerous Arizona Cardinals.
After overhauling their receiving corps, two things remain the same, and my Cardinals vs Bills predictions are bullish on one particular Bills player.
Find out why James Cook is my focus in my NFL picks for Sunday, September 8.
Cardinals vs Bills prediction
My best bet
James Cook Over 82.5 rushing + receiving yards (-118 at BetMGM)
My analysis
Jump onboard the James Cook hype train with me here as the Buffalo Bills offense walks into a favorable Week 1 matchup against an Arizona Cardinals defense that ranked last in DVOA in 2023.
It’s no secret that Cook was one of the big winners when Joe Brady replaced Ken Dorsey as Buffalo's offensive coordinator in mid-November, emerging as an ideal every-down complement to Josh Allen.
Cook averaged 17 carries in his next six contests, along with a steady receiving role, on the way to a Pro Bowl selection – and, if anything, he’s poised for an even bigger workload entering his third year in the league.
It’s a different cast of characters with Allen in the receiver room this season. Sure, tight ends Dawson Knox and Dalton Kincaid are back and slot receiver Khalil Shakir returns, but the Bills said goodbye to Stefon Diggs and Gabe Davis. The often-injured Curtis Samuel and rookie Keon Coleman will be asked to fill those spots.
That adds up to plenty of unknowns for Buffalo, making Cook a welcome security blanket for Allen as a shifty runner and a check-down option.
Of course, it helps that the Cardinals arrive with major defensive flaws and no evidence to suggest they’ve fixed their porous run defense. Arizona allowed a league-worst 143.2 yards per game on the ground in 2023.
Coupled with a limited pass rush, the visitors aren’t likely to put up much of a fight at the line of scrimmage, and I see Cook jumping out to an impressive start here.
Cardinals vs Bills same-game parlay
James Cook Over 59.5 rushing yards
James Conner anytime TD
Bills -6.5
I’m carrying over the rushing yards portion of my Cook best bet into this SGP and loading up with his opposite number, James Conner, who’s also in a favorable spot as the Buffalo run defense tries to patch over the injury to Matt Milano.
I like the odds for an anytime Conner touchdown. He’s going to get the lion’s share of the backfield work for Arizona, and he finished with nine touchdowns in 13 games last year, including five in his final five contests.
The Cardinals’ game plan should start with a heavy dose of the ground game, even with the temptation to test Buffalo’s Damar Hamlin in his first start since his cardiac arrest in January 2023, and the threat of Murray should ease the attention on Conner in the red zone.
I’m also riding with Buffalo to cover a spread that’s dipped below a touchdown margin. Again, it comes back to the Cardinals’ defensive woes, and it’s asking a lot for this Arizona offense to bail them out, even with the threat of Marvin Harrison Jr. and Trey McBride.
Though the Bills are 9-12 ATS at Highmark Stadium over the past two seasons, this is set up for Allen to show why he’s still an MVP candidate. As long as he can stay patient in the pocket, the hosts have more cards to play.
Learn how to bet a same-game parlay with these helpful tips and strategies.
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Cardinals vs Bills odds
Cardinals vs Bills live odds
Cardinals vs Bills opening odds
- Spread: Arizona +7 | Buffalo -7
- Moneyline: Arizona +260 | Buffalo -302
- Over/Under: Over 48 | Under 48
Odds courtesy of BetMGM
Cardinals vs Bills spread and Over/Under analysis
- Though Buffalo has lost two of its past three Week 1 contests, the hosts finished the 2023 regular season with five straight victories to reach the playoffs.
- The Cardinals have only covered the first-half spread in seven of their past 20 outings, and this is a team that’s coming off back-to-back 4-13 seasons.
- The Bills hit the 2Q Over in nine of their final 10 games last year, but the Under was 11-8 last season for Allen & Co., including the playoffs.
- It’s tough to look past the Over on a total of 47.5, with both defenses looking vulnerable, and Arizona gave up almost 27 ppg last year.
Cardinals vs Bills betting trend to know
The Bills won outright in 10 of the 14 games where they were favored in 2023. Find more NFL betting trends for Cardinals vs. Bills.
Cardinals vs Bills game info
| Location: | Highmark Stadium, Orchard Park, NY |
| Date: | Sunday, 9-8-2024 |
| Kickoff: | 1:00 p.m. ET |
| TV: | CBS |
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