Arizona Cardinals vs. Buffalo Bills Week 1: Promos, Odds, Predictions, Picks & Best Bets

The Bills’ moneyline odds imply that they should easily handle the Cardinals, so we’re trusting them to win at home.

Buffalo is a Super Bowl dark horse, but there are plenty of holes on Sean McDermott’s team, with the largest coming via a training camp injury to Matt Milano.

Milano is regarded as the leader of the Bills’ defense, but he hasn’t been on the field since Week 5 of the 2023 season. He suffered a grueling season-ending leg injury last year and then injured his bicep during training camp.

Milano could potentially return in December, but it’s too early to tell. As we saw last season, Buffalo isn’t as good on defense without Milano. Additionally, they’ll also need to adjust to life without Stefon Diggs and Gabe Davis on offense.

Diggs didn’t produce much for the Bills in 2023, but he was still an explosive threat for Josh Allen. Buffalo will need to make some adjustments to account for his absence, but it’s still a much better team than Arizona.

The Cardinals aren’t great on defense, and their offense revolves around a rookie making his NFL debut. We’re backing the Bills moneyline, but the high price makes us look to the spread for a more viable betting option.

Buffalo is a 6.5-point home favorite, and we believe it will cover the spread. We would play this up to seven points.

It’s hard to tell much based on the NFL preseason, but it does give a small indication of a team’s potential when the starters are in the game.

Arizona’s starters weren’t perfect in the preseason, especially on the defensive side of the ball as the Cardinals went 0-3 and gave up 75 combined points. This is nothing new, however, as their defensive woes were present throughout 2023 as well.

Arizona allowed 26.8 points per game last season (31st in NFL) en route to a 4-13 record and didn’t improve much in the offseason. Now, it must face one of the league’s best quarterbacks in Allen. He has turnover problems, sure, but he also threw for 4,306 yards, rushed for 524 yards and had a combined 44 touchdowns last season.

This total of 47 is very high for Week 1 since defenses are usually ahead of offenses early in the season, but we don’t anticipate that being the case in this game. We recommend playing the Over up to 49 points.

Arizona’s scoring defense was second-worst in the NFL last season, struggling both on the ground and through the air. The Cardinals surrendered the most rushing yards in the NFL and yielded a whopping 32 passing touchdowns (third-most).

Allen should have a field day. We believe Buffalo will call many designed quarterback runs to take advantage of Arizona’s weak rushing defense, which should lead to plenty of points for the Bills.

Meanwhile, Buffalo’s defense will also continue to miss Milano. While the Cardinals may not have many sustained drives, they have explosive players who can get the ball in the end zone. Murray is a dual-threat quarterback like Allen, and Harrison Jr. can beat the Bills’ secondary over the top.

If Buffalo doesn’t get pressure, Arizona should score enough to help hit the Over.

Josh Allen Anytime Touchdown (-125)

Allen proved he’s arguably the best rushing quarterback in the league last year outside of Lamar Jackson, posting one of the best seasons of his career. Not only did the Bills use Allen in the designed run game while still protecting his body, but he was also excellent at scrambling under pressure and creating big gains.

His rushing yards total is 31.5, but we’re staying away from this line. We believe Allen will have a lot of success in the pocket, so he may not run as consistently. That said, he is a run-first player around the goal line, and we believe he will find the end zone.

James Conner Over 53.5 Rushing Yards (-120)

The Cardinals’ goal in Week 1 will be to slow the game down and keep the ball out of Allen’s hands as much as possible. James Conner leads Arizona’s backfield, and he doesn’t get enough credit for his dominance.

Conner was 21st in carries last year but had the sixth-most rushing yards in the NFL (1,040). He averaged five yards per carry despite running behind a flawed offensive line.

Without Milano in the middle of Buffalo’s defense, Conner should have success running the football this week.

• Bills Moneyline (-298): The Bills have the superior team and home-field advantage. The Cardinals’ biggest weakness is their defense, and they have to face one of the best quarterbacks in the game. Allen should be productive all afternoon and lead Buffalo to a win.
• Bills -6.5 (-112): The Bills can win this game by double digits if they play well. The Cardinals have high hopes but also have holes in their roster. It will be hard for them to stay within a touchdown against a team as good as Buffalo.
• Over 47 (-110): The Bills had one of the best offenses in the NFL last season. It’s tough to defend Allen, so we expect him to create points. The Cardinals should also have success on offense and should get some explosive plays from Murray, Conner and Harrison Jr.
• Josh Allen Anytime Touchdown (-125): Allen’s anytime touchdown odds are short for a quarterback. However, that’s because he is coming off a career touchdown season, which should continue. The Bills work many designed quarterback runs around the goal line, which should pay off against the Cardinals.
• James Conner Over 53.5 Rushing Yards (-120): The Cardinals should try to slow their season opener down. Their best offense is keeping Allen off the field, and they will try do so with Conner.

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