Cardinals vs. Chargers Prediction, Odds, Spread, Injuries, Trends for NFL Week 1

It feels like if the Los Angeles Chargers are going to take the next step and become true Super Bowl contenders, it's going to happen this year. Their team is healthy, Justin Herbert is reaching his prime, and offensive mastermind, Mike McDaniel, has taken over as their Offensive Coordinator.

They'll begin their 2026 NFL campaign against the Arizona Cardinals, who have the lowest win total in the NFL heading into this season.

Let's dive into the odds and my best bet for this Week 1 interconference showdown.

Cardinals vs. Chargers Odds, Spread, and Total

Odds via FanDuel Sportsbook

Spread

Cardinals +9.5 (-105)
Chargers -9.5 (-115)

Moneyline

Cardinals +410
Chargers -550

Total

OVER 47.5 (-102)
UNDER 47.5 (-120)

Cardinals vs. Chargers How to Watch

Date: Sunday, September 13
Time: 4:25 PM ET
Venue: SoFi Stadium
How to Watch (TV): CBS
Cardinals record: 0-0
Chargers record: 0-0

Cardinals vs. Chargers Betting Trends

The Chargers are 3-3 against the spread in their last six games vs. the Cardinals
The OVER is 4-2 in the last six meetings between these two teams
The Cardinals went 2-8 ATS in their last 10 games in 2025
The Chargers went 5-5 ATS in their last 10 games in 2025

Cardinals vs. Chargers Key Player to Watch

Justin Herbert, QB - Los Angeles Chargers

Everything is looking up for Justin Herbert heading into this season. He has a new offensive coordinator in Mike McDaniel, and maybe more importantly, his two starting offensive tackles are healthy. If things break his way, he could be an MVP candidate this season. He threw for 3,727 yards, 26 touchdowns, and 13 interceptions last season.

Cardinals vs. Chargers Prediction and Best Bet

In the Week 1 edition of the Road to 272 Bets, I broke down why I'm betting the OVER in this game:

I simply can't get behind a double-digit favorite in a Week 1 game. That has disaster written all over it, especially with seemingly every year there being one major upset in the opening week. That's why, instead of a side in this one, I'm going to look to the total and bet the OVER.

The Chargers' offense may be entering its peak this season. Joe Alt and Rashawn Slater are healthy, and now Mike McDaniel takes over as offensive coordinator. This could be one of the most fun offenses to watch in football this season. Meanwhile, the Chargers' defense will have to try to move on from defensive coordinator Jesse Minter, who is now the head coach of Baltimore. It may take them a few weeks to hit their stride.

For the Cardinals, I have a lot of concerns about their defense, which was one of the worst in the league a season ago, but you can't deny the fact that they have some weapons on offense. Between Marvin Harrison Jr., Michael Wilson, Trey McBride, and a one-two punch in the backfield between Jeremiyah Love and Tyler Allgeier, they can move the ball down the field.

I'll sit back and root for points in this one.

Pick: OVER 47.5 (-102) via FanDuel

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