Arizona Cardinals vs. New Orleans Saints Picks and Prediction, Sunday, September 7, 2025
Arizona Cardinals (0-0) vs. New Orleans Saints (0-0)
Week 1 of the 2025 NFL season brings plenty of interesting matchups, including the NFC showdown at Caesars Superdome in New Orleans, LA, on Sunday afternoon, so we have prepared the Cardinals vs. Saints prediction and the latest odds update.
The Saints start the Kellen Moore era in front of the home audience. They are 6.5-point underdogs with a total of 43.5 points. New Orleans meets Arizona for the first time since 2022, when the Cardinals beat the Saints 42-34 as 2.5-point home favorites.
Read more about this Cardinals vs. Saints prediction, and check out all our NFL picks for Week 1. The kick-off at Caesars Superdome is set at 1:00 PM ET.
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The Cardinals desperately need more from Kyler Murray
The Arizona Cardinals haven’t won a playoff game since the 2015 NFC Divisional Round. They’ve made it to the playoffs just once in the last nine years, and the Cardinals will need a strong performance from Kyler Murray to get back to the postseason.
Arizona enters Year 7 of the Kyler Murray era, and it’s fair to say that the former No. 1 pick has been a disappointment thus far. Last year, the Cardinals went 8-9, and Murray threw for 3,851 yards, 21 touchdowns, and 11 interceptions while rushing 78 times for 572 yards and five touchdowns. Arizona ranked 12th in scoring offense (23.5 points per game) and 15th in scoring defense (22.3).
The Cardinals hope for a sophomore surge from wideout Marvin Harrison Jr., who posted 62 catches for 885 yards and eight touchdowns in his rookie season. Tight end Trey McBride will look to build on his tremendous 2024 campaign (111 receptions for 1,146 yards and two scores), while James Conner returns at running back after tallying 1,508 yards from scrimmage and nine touchdowns in 2024.
Arizona will have to improve on the other side of the ball, too. The Cardinals’ defense ranked 20th in rushing yards (126.4 per game) and 14th in passing yards (216.1) this past season. Arizona was 26th in quarterback hits (76) and tied for 13th in sacks (41).
The Cardinals signed edge rusher Josh Sweat in the offseason, and the former Eagle should be a huge reinforcement. They also added veterans Calais Campbell and Dalvin Tomlinson to fortify their defensive line.
The Saints hope for a successful first year under Kellen Moore
The New Orleans Saints went 5-12 last season. They fired Dennis Allen in November after seven losses in a row, and the special teams coordinator, Darren Rizzi, led the team for the rest of the year. The Saints were scoring 19.9 points per game (tied for 24th in the NFL) while surrendering 23.4 points in return (19th).
New Orleans struggled with injuries in 2024. Derek Carr started just 10 games and posted a 5-5 record, throwing for 2,145 yards, 15 touchdowns, and five interceptions. Carr announced his retirement in the offseason, and the Saints named Spencer Rattler as their starting quarterback for the 2025 season.
Rattler was selected by the Saints in the fifth round of the 2024 NFL Draft. He was 0-6 in six starts last season, tossing for 1,317 yards, four touchdowns, and five interceptions. The Saints drafted Tyler Shough in the second round this past spring, and he’ll serve as a backup.
The Saints have high expectations for Kellen Moore, who’s been one of the most dynamic offensive coordinators in the league over the last few years. Last season, Moore won the Super Bowl with the Philadelphia Eagles, and maybe he can help Rattler improve his game.
New Orleans will continue to lean on Alvin Kamara, who rushed for 950 yards and six touchdowns in 2024. Kamara also had 68 receptions for 543 yards and two scores. WR Chris Olave played just eight games last season due to injuries, and he’s probably the best weapon in this offense.
On the other side of the ball, the Saints lost some very important players, but replaced them with quality veterans. Brandon Staley is a new defensive coordinator, and the former Chargers head coach will prioritize pass defense.
Cardinals vs. Saints Pick
| # | Handicapper | Profit |
|---|---|---|
| 1 |  Earle Sports Bets | +2,298.00 |
| 2 |  Ross Benjamin | +1,840.00 |
| 3 |  Rob Vincilleti | +1,757.00 |
| 4 |  David Hess | +1,745.00 |
| 5 |  Dan Kaiser | +987.00 |
Spread Pick for Arizona Cardinals vs. New Orleans Saints
- New Orleans Saints +6.5 (5 units)
I expect the Cardinals to beat the Saints, but covering a 6.5-point spread on the road might be a tall task for Kyler Murray and his teammates. Arizona lacks the firepower to dominate New Orleans in the trenches, and the Saints will find a way to move the ball and make enough stops to keep it close down the stretch.
I know it’s hard to trust Spencer Rattler, but I also have to see some improvement from the Cardinals’ pass rush. Moreover, the Saints have a top-notch running back in Alvin Kamara, who is a great catcher out of the backfield.
The Cardinals are winless in four straight outings on the road. They’ve gone 0-4 SU and ATS in their previous four road games when listed as favorites, while the Saints are 2-3 SU and 3-2 ATS in their last five showings at home as underdogs.
Over/Under Pick for Arizona Cardinals vs. New Orleans Saints
- Under 43.5 (5 units)
We shouldn’t see a firecracker at Caesars Superdome in Week 1. These two defenses look vulnerable against rushing, so I expect both teams to pound the rock and eat the clock. New Orleans ranked 31st in the NFL in rushing yards allowed per game in 2024, and the Cardinals will feed James Conner all day long. The Saints need to put the ball in Alvin Kamara’s hands and lift some pressure off their young quarterback.
The under is 5-1 in the Saints’ last six games overall and 4-1 in their previous five outings at home. Also, the under is 7-2 in the Cardinals’ last nine showings on the road as favorites.
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