The Arizona Cardinals and Los Angeles Chargers will face off in NFL Week 1 this afternoon. Kickoff is set for 4:25 p.m. ET from SoFi Stadium in Inglewood, Calif. The game will broadcast live on CBS.
The Chargers are 9.5-point favorites over the Cardinals on the spread (Chargers -9.5), with the over/under set at 47.5 total points. Los Angeles is a -490 moneyline favorite to win outright, while Arizona is +380 to pull off the upset.
Let's get into my Cardinals vs Chargers predictions and NFL picks for Sunday, September 13.
My Cardinals vs Chargers Prediction
- Cardinals vs Chargers pick: Chargers -9.5
My Cardinals vs. Chargers best bet is on Los Angeles to cover the spread, with the best price currently available at FanDuel. Make sure to find the best odds by checking our live NFL odds page and to download the Action Network app to get the latest betting analysis and picks.
Cardinals vs Chargers Odds
| Cardinals Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
+9.5 -115 | 47.5 -104o / -118u | +380 |
| Chargers Odds | ||
|---|---|---|
| Spread | Total | Moneyline |
-9.5 -105 | 47.5 -104o / -118u | -490 |
Cardinals vs Chargers NFL Week 1 Preview
Arizona Cardinals Betting Preview
The Cardinals failed to make any major changes in their personnel on defense and new head coach Mike LaFleur elected to retain defense coordinator Nick Rallis.
Rallis’ unit played poorly a season ago, to put it lightly.
Opposing offenses scored points on 49% of their offensive possessions against the Cardinals — only one defense fared worse league-wide. Arizona struggled to stop the run — ranking 28th in EPA/play against the run and failing to generate a consistent pass rush — ranking 27th in pressure rate at 31%.
This defense has a tall task ahead of them as Chargers offensive coordinator Mike McDaniel is one of the most skilled playcallers in the NFL when it comes to marrying his rush offense with the play-action pass.
McDaniel usually hovers around the 30% mark in his use of play-action, one of the higher rates for any offensive coordinator in the NFL. His heavy use of pre-snap motion and zone rushing concepts will give the Cardinals' defense fits. Arizona ranked 29th in yards per carry allowed last year in defending zone-based rushing concepts.
In 2025, opposing offenses had a passing success rate of 53% against the Arizona pass defense. That was the fourth-worst mark in the league and each team worse than the Cardinals in that category was able to generate more sacks, as they tallied just 30 the entire season.
The question then becomes if Jacoby Brissett can lead a highly skilled group of receivers (Marvin Harrison Jr., Trey McBride, Michael Wilson) and runners (Jeremiyah Love, Tyler Allgeier) to match the scoring opportunities for Arizona.
Los Angeles Chargers Betting Preview
Los Angeles finds itself as a substantial favorite at home against a Cardinals team that finished 2025 with a 3-14 record while also having one of the league’s worst defenses.
Justin Herbert should carve up this secondary as he will enjoy a level of protection from his offensive line he did not have a season ago — both of his tackles, Joe Alt and Rashawn Slater, are healthy and in the starting lineup. McDaniel will be able to engineer several productive scoring drives in this game.
The Chargers defense will look different without Jesse Minter as defensive coordinator, but it is nearly impossible to predict if they can replicate their success as one of the three best pass defenses on the level of the Seahawks and Texans from a season ago.
Their ability to potentially shut down Brissett will obviously aid them in gaining an early lead in this game, but it will also stymie any potential backdoor cover attempt by the Cardinals in the fourth quarter.
Cardinals vs Chargers Prediction, Betting Analysis
There are plenty of relevant trends when looking at a matchup with this big of a number early in the season.
Looking through the entirety of Bet Labs’ data (dating back to 2003), favorites of more than a touchdown have performed poorly against the number in Week 1 — home teams of more than 7 points are 14-25 against the spread (ATS), covering at a 35% rate.
However, Chargers head coach Jim Harbaugh has been a wagon in the month of September. Not only have Harbaugh’s squads covered the number at a 66% rate during the first month of each season, but he also remains unbeaten straight up and against the spread in Week 1 since he has taken over as the head man for Los Angeles.
My instincts lead me to simplify this handicap by fading the clear-cut worst unit on the field — the Arizona defense.
I will take my chances backing the team I know will light up the scoreboard. Brissett and company will have to prove me wrong, but this isn’t the spot they will do so.
Pick: Chargers -9.5 (-105; Fanduel)
Spread
As mentioned, I'm backing Los Angeles to cover the spread.
Moneyline
I will not be betting on either side of the moneyline.
Over/Under
I'm also staying away from game totals.
