Bills Vs Cardinals Odds Overview
👇Take a look at this table which summarizes the key betting details for the Week 1 clash.
| ⭐ Favorite | Bills |
| ⚖️ Bills Win | 78% Chance |
| 🔢 Point Spread | BUF -7 |
| 📊 Moneyline | BUF -355 |
| 📈 Game Total | O/U 48 |
| ✅ Last Verified | June 11, 2025 |
👇It’s also essential to consider the anticipated player lineups, the weather conditions, and the game location for this opening week matchup.
Evaluating the Betting Odds for Bills vs. Cardinals.
Bills vs Cardinals Injury Report
Who is Favored to Win?
According to Draftkings and otherSportsbooks in Ontario The Buffalo Bills are favored by 7 points against the Arizona Cardinals for their Week 1 encounter. Keep in mind that these odds may fluctuate, so it’s wise to compare offers across different sportsbooks.
Bills Chances To Win vs Cardinals
The Bills have been listed as 6.5-point favorites over the Cardinals in the opening week. The game total is projected to be 48 points. With Kyler Murray back to full health and the talented rookie Marvin Harrison Jr. impressing during training, the Cardinals’ offensive strategy remains an open question. The Bills, having made the playoffs five years in a row and dominating the AFC East, rightfully hold strong favoritism in this matchup.
How The Bills Win vs Cardinals
The Bills are likely to win against the Cardinals if they can exploit their notably weak secondary . Last season, the Arizona Cardinals had a troubling 68.58% completion rate against them, ranking as the second worst in the league. Buffalo, on the other hand, boasts a highly skilled quarterback in Allen. However, with a career-high 18 interceptions last season, it will be crucial for him to maintain control of the ball to secure a victory.
Fromdeereplanet.com
How The Cardinals Win vs Bills
On the contrary, while the Cardinals may struggle to contain the Bills' dynamic offense led by Allen, they can aim to match their pace . In his second NFL season, Murray threw for 3,971 yards and secured 26 touchdowns despite his injury setbacks. The Cardinals' chances hinge on getting Harrison Jr. involved early on, capitalizing on the Bills' defensive weaknesses in the secondary.
History of Bills vs Cardinals Games
Throughout history, the Cardinals and Bills have faced off infrequently due to their placements in the NFC West and AFC East. They've only met in 12 cross-conference games. The Bills currently hold a 7-5 advantage in the series and have claimed victory in six of the last eight encounters.
Memorable Matchups Between the Bills and Cardinals.
The most recent meeting between these teams took place on November 15, 2020 . Since the end of the 2012 season, there have only been a couple of matchups. The Cardinals won three out of the initial four games but have had less success in recent times. Despite the limited frequency of their encounters and no playoff meetings, this Week 1 matchup is bound to draw interest amidst Buffalo's favored status.
Game 1: Nov. 15, 2020 - Cardinals 32, Bills 30
Like the upcoming Week 1 game, their past matches involved Josh Allen and Kyler Murray. In one such game, Allen threw two pivotal interceptions and the Bills’ rushing attack faltered. Nevertheless, Allen amassed 284 passing yards, scoring points in every quarter, while the Cardinals rallied with 17 points in the third period. Murray contributed with 245 passing yards, and the teams combined for over 200 yards rushing. It was an electrifying game between two competitive teams.
Game 2: Oct. 14, 2012 - Bills 19, Cardinals 16
Though not as thrilling, this essential matchup is the only one of the 12 that required overtime. The Bills began with Ryan Fitzpatrick at quarterback and had Kevin Kolb leading the Cardinals. Arizona held a 4-2 record at that time, but their season ended poorly at 5-11. The teams focused on their rushing attacks, with the Bills accumulating 165 yards from 33 attempts and two touchdowns, while the Cardinals recorded 182 rushing yards.
Game 3: Sept. 21, 1986 - Bills 17, Cardinals 10
There are limited choices, but this matchup featured the iconic Jim Kelly before the Bills transformed into a powerhouse during the 1990s. Kelly faced difficulties with only 10 pass attempts for 105 yards. Though both sides relied on the run game, neither managed to surpass 125 yards. This game is primarily noted for Kelly's presence and marks a moment before the team’s rise to prominence.
History of the Bills Vs Cardinals
Here’s a record of the Bills' encounters with the Cardinals:
| Date | Buffalo Bills Score | Location | Cardinals Score | Result |
| 11/15/2020 | 30 | @ Arizona Cardinals | 32 | L |
| 9/25/2016 | 33 | vs. Buffalo Bills | 18 | W |
| 10/14/2012 | 19 | @ Arizona Cardinals | 16 | W |
| 10/05/2008 | 17 | @ Arizona Cardinals | 41 | L |
| 10/31/2004 | 38 | @ Buffalo Bills | 14 | W |
| 12/19/1999 | 31 | @ Arizona Cardinals | 21 | W |
| 11/11/1990 | 45 | @ Buffalo Bills | 14 | W |
| 09/21/1986 | 17 | @ Buffalo Bills | 10 | W |
| 09/09/1981 | 7 | @ St. Louis Cardinals | 37 | L |
| 11/15/1981 | 0 | @ St. Louis Cardinals | 24 | L |
| 11/27/1975 | 32 | @ St. Louis Cardinals | 14 | W |
| 10/31/1971 | 23 | vs. St. Louis Cardinals | 28 | L |
The Bills and Cardinals have gone head-to-head 12 times, with the Bills leading the series 7-5.
Related Content on Buffalo Bills Betting:
Bills Vs Cardinals FAQ
Indeed, the Bills are projected to defeat the Cardinals by a touchdown in Week 1.
The Buffalo Bills will face the Arizona Cardinals in their opening week contest.
Author
Brandon Justice brings nearly ten years of experience in sports and betting coverage, specializing in college football, college basketball, NFL, and MLB. His aim is to provide in-depth analysis of sports betting trends and data based on extensive experience, including contributions to The Action Network and Rivals.com.
