It’s an NFC West showdown as the Arizona Cardinals (2-0) face the San Francisco 49ers (2-0). Here are the odds, predictions, and free expert picks for the Cardinals vs. 49ers.
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Cardinals vs. 49ers: Game Information
red for the road trip 🔴 pic.twitter.com/SmZktWalvJ
— Arizona Cardinals (@AZCardinals) September 18, 2025
- 🏈 Game: Cardinals vs. 49ers
- 🕗 Time: 4:25 p.m. ET
- 🏟 Location: Levi’s Stadium — Santa Clara, California
- 📺 TV Channel: Fox
- 💻 Live Stream: Fox One, NFL+
Cardinals vs. 49ers Odds, Predictions, and Picks
Back to our roots 🏡 pic.twitter.com/KpNdE0z3QZ
— San Francisco 49ers (@49ers) September 18, 2025
You can only play those who are on the schedule. That best describes the Cardinals’ undefeated start. Arizona has wins over the New Orleans Saints and the Carolina Panthers, two teams that will almost certainly finish below .500.
The Cardinals took advantage of an inferior Saints team in Week 1 to win 20-13.
In week 2, the Cardinals built a 27-3 lead in the third quarter, but they almost blew it at the end. After the Panthers scored to cut it to 27-22, Carolina recovered an onside kick.
However, a Calais Campbell sack late ended all hopes of a Carolina comeback.
San Francisco started the season off with two road victories. The 49ers needed late-game heroics to defeat the Seahawks 17-13 in Week 1.
Without Brock Purdy and George Kittle, Mac Jones and Jauan Jennings led the way for San Francisco in their 26-21 win over the Saints.
Jones finished 26 of 39 for 279 yards and three touchdowns, including one to Jennings. Kyle Shanahan reportedly wanted to take Jones in the 2021 draft before ultimately selecting Trey Lance.
Shanahan has a losing record against the Cardinals (7-9). However, Murray is only 4-4 against the 49ers.
The 49ers have the better passing defense (166.0 passing yards allowed vs. Arizona’s 255.5).
I like that the 49ers have been tested by a good team (Seattle) and won. With the margins so close, I’ll take the 49ers by a field goal at home.
Pick: 49ers -2.5 (-115)
Cardinals vs. 49ers Prop
Kyle Shanahan says Christian McCaffrey is far and away the best receiving running back he’s ever coached
This was McCaffrey’s response: pic.twitter.com/EyLdfy5Z14
— Kevin Krueger (@kevinkruegs) September 18, 2025
Christian McCaffrey has looked healthy to start the season.
The versatile McCaffrey’s stats through two games: 124 rushing yards, 125 receiving yards, and one receiving touchdown.
While the Cardinals have been good at stopping the run (78.0 yards per game, 6th in the NFL), they rank 26th against the pass (255.5).
With Kittle and Aiyuk out, Jones will be looking to check down to McCaffrey frequently. McCaffrey hit his receiving total in two consecutive weeks. Let’s make it three.
