Cardinals vs. Chargers Prediction: Week 1 Odds, Picks & Best Bet
We're almost ready to watch a pair of re-tooled offenses go head-to-head, led by OC Mike McDaniel and head coach Mike LaFleur, so let's find out which bets to place with my Cardinals vs. Chargers prediction.
This game kicks off at 4:25 p.m. ET from SoFi Stadium in Inglewood, Calif. (CBS). The Chargers are entering this matchup as a large -9.5 point betting favorite.
🏈 Cardinals vs. Chargers picks & predictions
See all of our experts' NFL picks for Week 1 based on the latest NFL odds.
| Pick | Bet size |
|---|---|
| Cardinals +9.5 (-105 via DraftKings) | 1.05 units |
| Over 47.5 (-102 via DraftKings) | 1.02 units |
Total wagered: 2.07 units | Max profit: +2.0 units
💰 Cardinals vs. Chargers prediction & best bet
Check out all of our NFL picks for more analysis across this week's slate.
Cardinals +9.5(-105 via DraftKings)
The Mike LaFleur era begins in Arizona, while Mike McDaniel is back to his roots, landing with as the Chargers' new OC. It makes sense, considering both of these offenses finished 2025 20th or worse in points scored per game.
Football fans are waiting on Chargers QB Justin Herbert to take the next step. McDaniel was hired to be the key to unlocking this progression.
Brissett finished 2025 with huge production, posting a 64.9 percent completion rate with 3,366 yards, 23 touchdowns, and just 8 interceptions. The Chargers' defense is largely intact from 2025, which finished as a top-10 scoring unit (20.0/game).
Since opening at +11.5, the Cardinals have moved down to +9.5. I'd prefer getting +10.5 through a key number, but this line still feels like too much.
Third-year wideout Marvin Harrison Jr. needs to step up. Fortunately, rookie RB Jeremiyah Love, star TE Trey McBride, and newly paid WR Michael Wilson have enough talent to move the sticks against Jim Harbaugh's defense.
Bet on the Cardinals' +9.5 at -105 odds on DraftKings.
📡 SBR Edge: Coverin' Cardinals
The Cardinals have covered +9.5 in 3 of the last 4 head-to-head matchups against the Chargers, including 2 outright wins.
Fireworks erupt from new playcallers
The Cardinals have a new RB1, two strong wide receivers, and a star tight end to target in the passing attack. LaFleur may lean into Love's physicality early, as he was the OC under Sean McVay during the Rams' run-centric success over the last three seasons. This could set up Brissett for effective downfield targets on play-action passes.
Herbert's going to find himself thriving in a new offense. Especially against the Cardinals' defense, which lacks a lot of big-name players under fourth-year DC Nick Rallis. Arizona finished 28th in points allowed in 2025 (28.7) and opted to focus on its offense this offseason.
This game will be a track meet, with the Chargers crossing the finish line in a 31-23 win.
Score prediction: Chargers 31, Cardinals 23
📊 Cardinals vs. Chargers odds
See the latest NFL odds for every Week 1 matchup.
Cardinals vs. Chargers opening odds
•Moneyline: Cardinals +460 | Chargers -625
•Spread: Cardinals +11.5 (-115) | Chargers -11.5 (-105)
•Over/Under: Over 46.5 (-112) | Under 46.5 (-108)
📺 How to watch Cardinals vs. Chargers: Week 1
- Date: Sunday, Sept. 13
- Kickoff: 4:25 p.m. ET
- Location: SoFi Stadium (Inglewood, Calif.)
- TV: CBS
📃 Affiliate disclosure
Sportsbook Review may receive a commission if you sign up through our links. Not intended for use in MA. Bonuses not applicable in Ontario. 21+ only. (Gambling problem? Call 1-800-GAMBLER)
Related Articles
