The Arizona Cardinals and Los Angeles Chargers kick off their regular-season schedule on Sunday in Inglewood, California. Kickoff from SoFi Stadium is at 4:25 p.m. ET (CBS). Let's analyze NFL odds around the Cardinals vs. Chargers odds and make our expert NFL picks and predictions for the best bets.
The Cardinals open the season with first-year head coach Mike LaFleur, who took over a team that was 3-14 last season. QB Jacoby Brissett is the starter after Kyler Murray was released in the offseason. They added RB Tyler Allgeier in free agency and selected RB Jeremiyah Love third overall in this year's draft. Oddsmakers have them among the lowest teams in the league in terms of projected win total.
The Chargers, with head coach Jim Harbaugh in his
third season, have been to the playoffs two straight years with first-round exits. After former defensive coordinator Jesse Minter left to be the Baltimore Ravens' head coach, Chris O'Leary was promoted to replace him. Former Miami Dolphins head coach Mike McDaniel replaces Greg Roman as offensive coordinator. QB Justin Herbert remains their starter.
The Chargers lead the all-time series 11-5 against the Cardinals and are 7-1 at home, but the Cardinals won their last meeting, a 17-15 win in Glendale, Arizona, in 2024 as 1.5-point underdogs with the Under (44.5) cashing.
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Cardinals at Chargers odds
Provided by BetMGM Sportsbook; access USA TODAY Sports Scores and Sports Betting Odds hub for a full list. Lines last updated Saturday at 5:15 p.m. ET.
- Moneyline (ML): Cardinals +380 (bet $100 to win $380) | Chargers -500 (bet $500 to win $100)
- Against the spread (ATS): Cardinals +9 (-108) | Chargers -9 (-110)
- Over/Under (O/U): 47.5 (O: -108 | U: -110)
Cardinals at Chargers key injuries
Cardinals
- OL Isaiah Adams (knee) out
- RB Jeremiyah Love (ankle) questionable
- S Dadrion Taylor-Demerson (ribs) out
- CB Garrett Williams (Achilles) out
Chargers
- OLB Tuli Tuipulotu (hip) questionable
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Cardinals at Chargers picks and predictions
Prediction
Chargers 31, Cardinals 20
Moneyline
The Cardinals have not their first game with a new head coach since Don Coryell in 1973. They lost their final 9 games last season, allowing 37 points or more six times. They have the same questions about the pass rush, pass coverage and run defense as they did a year ago, and the Chargers, even with their offensive struggles in 2025, now have one of the most productive play-callers in the NFL in McDaniel.
The Chargers were a top 10 defensive unit last season in yards, points, first downs allowed, pass defense and run defense. The Cardinals have promise offensively, but the Chargers are too strong on both sides of the ball.
Expect a Chargers win, but with -500 odds, you get almost no value with the moneyline.
PASS.
Against the spread
The Chargers are a bad matchup for the Cardinals. Their new offensive scheme will be very tough for the Arizona defense to slow. Herbert has averaged more than 310 passing yards and has three touchdown passes with no interceptions in two career games against the Cardinals.
The Chargers also have the defense to not allow Arizona's promising offense to thrive. Plus, the Cardinals lost by more than 2 scores 6 times in their final 9 game of last season.
BET CHARGERS -9 (-110).
Over/Under
Four of the Cardinals' final 5 regular-season games last season had totals above 47. Including the preseason, they have allowed over 30 points 9 times in their last 13 games.
The Cardinals scored 17 or more in 13 of their last 14 games in the regular season, as well.
BET OVER 47.5 (-108)
Best prop bet
Jacoby Brissett OVER 1.5 passing TDs (+150)
Brissett threw 2-plus TD passes in 10 of his 12 starts last season. The passing game was good with him at quarterback, and he has reliable pass catchers in TE Trey McBride, WR Marvin Harrison Jr. and WR Michael Wilson.
Betting odds calculator
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This article originally appeared on Sportsbook Wire: Arizona Cardinals at Los Angeles Chargers odds, picks and predictions
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