The Los Angeles Chargers are 9.5-point favorites against the Arizona Cardinals on Sunday, Sept. 13, in a 4:25 p.m. ET kickoff at SoFi Stadium.
My Cardinals vs. Chargers prediction breaks down whether Los Angeles can justify the hefty spread.
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Cardinals vs Chargers prediction: Chargers -9.5
I'd play the Los Angeles Chargers up to -11.5 because they have one of the NFL's best quarterback-coach duos in Justin Herbert and Jim Harbaugh.
Los Angeles has won 11 games in each of Harbaugh's first two seasons, and the Chargers are legitimate contenders in the Super Bowl odds.
That looks like a particularly significant advantage against the Arizona Cardinals, who enter the season with a bottom-five quarterback-coach combination in Jacoby Brissett and rookie head coach Mike LaFleur.
Arizona's 4+ total wins market at Kalshi is also the closest to a 50/50 probability among the available options. That said, the Chargers have been particularly dominant when facing weak competition under Harbaugh.
Since 2024, Los Angeles is 12-2 straight-up and 11-3 against the spread (ATS) vs. teams with a 40% winning rate or worse.
The Cardinals would need to finish 7-10 just to reach that 40% mark this season, making this historical matchup especially relevant.
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Cardinals vs Chargers combo
Low-key, Arizona has solid offensive weapons, including All-Pro TE Trey McBride, WR Michael Wilson, and former No. 4 overall pick WR Marvin Harrison Jr.
Also, I've said a bunch of times, "Blowouts are where Overs go to die," but the Cardinals were the kings of putting up meaningless points in garbage time last season.
They went 10-7 Over/Under with a +3.1 margin on the total.
Meanwhile, much to the chagrin of the football nerds, Harbaugh likes to "establish the run," and he knows Herbert needs to ground the game because he doesn't have many game-breakers to throw to.
Cardinals vs Chargers combo
- Chargers -9.5
- Over 47.5
- Los Angeles RB Omarion Hampton anytime touchdown
Cardinals vs Chargers touchdown scorer: Los Angeles RB Omarion Hampton
Despite being a former quarterback and having a top-10 NFL quarterback, Harbaugh is a relatively conservative playcaller with a balanced attack.
Chargers RB Omarion Hampton had just five touchdowns last season (four rushing and one receiving), but he only started six games.
Furthermore, Arizona's defense gave up the second-most rushing touchdowns to running backs last season and the fourth-most receiving touchdowns.
Since the Chargers didn't add any pass-catching options this offseason and they used a 2025 first-round pick on Hampton, I'm assuming he gets a larger role this season.
Cardinals vs Chargers odds
For help understanding probabilities, see our odds calculator.
- Spread: Cardinals +9.5 | Chargers -9.5
- Over/Under: Over 46.5 (55%) | Under 46.5 (50%)
- Moneyline: Cardinals 20% | Chargers 82%
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Cardinals vs Chargers weather
While not a traditional dome, SoFi Stadium in Los Angeles does have a roof with open sides. Regardless, the weather in LA Sunday will be roughly 80° with no chance of rain.
Check out our NFL weather page for up-to-date info on every matchup.
Cardinals vs Chargers trend to know
The Chargers are 4-1 ATS in their last five home games. Find more NFL betting trends for Cardinals vs. Chargers.
How to watch Cardinals vs Chargers
| Location | SoFi Stadium, Inglewood, CA |
| Date | Sunday, Sept. 13, 2026 |
| Kickoff | 4:25 p.m. ET |
| TV | CBS |
Cardinals vs Chargers latest injuries
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Odds are correct at the time of publishing and are subject to change.
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