Cardinals vs. Saints Final Score Prediction for NFL Week 1 (Arizona Should Dominate)

The Cardinals are massive favorites in Week 1.

The Arizona Cardinals are favored in Week 1. / Mark J. Rebilas-Imagn Images

The Arizona Cardinals are looking to get their 2025 season off to a strong start, as they are 6.5-point road favorites against the New Orleans Saints in Week 1. 

Kyler Murray and the Cardinals missed the playoffs in 2024 after a slow finish to the regular season, but they are looking to win the NFC West – which could be wide open – in the 2025 campaign.

Meanwhile, the Saints are in a rebuild with Spencer Rattler winning the starting job out of training camp/the preseason. Second-round pick Tyler Shough is waiting, but Rattler will look to improve upon a rookie season where he threw more touchdowns than picks across seven games (six starts).

This season at SI Betting, we’re attempting to predict the final score of each NFL game as a fun way to help bettors decide on the spread or total in their wagers. We’ll still have our game previews, props and more, but this is a fun way to potentially hit big on an exact score prediction.

So, using the latest odds and analysis for this game, here’s where I’m leaning on Sunday. 

Cardinals vs. Saints Odds, Spread and Total

Odds via DraftKings Sportsbook

Spread

• Cardinals -6.5 (-110)
• Saints +6.5 (-110)

Moneyline

• Cardinals: -285
• Saints: +230

Total

• 43.5 (Over -108/Under -112)

The Cardinals are one of the bigger favorites of the week against a Saints team that is widely expected to be the worst in the NFC.

New Orleans is starting Rattler, who did not win a single start (0-6) in the 2024 season. 

Cardinals vs. Saints Final Score Prediction

I don’t see the Saints hanging around in this game, unless Rattler is a totally different player than the one we saw a season ago.

New Orleans’ defense really faded in the 2024 season, allowing the fifth-most yards per play in the league, making it impossible for a banged-up offense to keep pace.

SI’s NFL betting insider Iain MacMillan shared his pick for this game earlier in the week in his Road to 272 column – where he picks every game of the NFL season:

The New Orleans Saints are projected to be the worst team in the NFL this season, and things didn't get better for them when they announced that Spencer Rattler has won the starting job at quarterback over their second-round round draft pick, Tyler Shough. Rattler went 0-6 as a starter last season, completing just 57% of passes, including four touchdowns and five interceptions.

When it comes to the Arizona Cardinals, they've typically been a good bet in September. Kyler Murray regresses as the season progresses, but he can rely on his athleticism more in the early weeks, leading to Arizona being a tough opponent in the first month of action.

With the spread set at below the magic number of seven, the Cardinals are a no-brainer.

I think Arizona wins this game going away, and the Cards are a great Survivor choice in Week 1. 

Final Score Prediction: Cardinals 27, Saints 10

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Odds refresh periodically and are subject to change.

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