The 2-0 San Francisco 49ers return home to Levi's Stadium to face off against the 2-0 Arizona Cardinals in their season home opener. Both teams will look to take first place in the NFC West, but if the 49ers plan to be number one, they must stick to these keys to victory.
Stop the Run
Expect the Cardinals to set the tone by establishing their run game. James Connor and Trey Benson will look to establish a ground-and-pound approach for the Cardinals. The 49ers' defensive front cannot allow the Cardinals' run game to break through for explosive plays. They gave up 121 yards to Alvin Kamara and the Saints last week.
Sunday will be Robert Saleh's first actual test against a mobile quarterback this season. Kyler Murray could be the X factor for the Cardinals' run game. The 49ers defense cannot forget the running ability of Murray. They must contain on the outside and keep someone over the middle if he decides to take off and run. If the 49ers' defense can stop the run, they will have a good chance of winning the game.
Limit Trey McBride
Trey McBride was the leading pass catcher for the Cardinals in 2024, and he continues to get high target volume in 2025. The 49ers' safeties struggled against Juwan Johnson of the New Orleans Saints in Week 2, giving up a touchdown.
Even if the defense allows McBride to create explosive plays, they must find a way to keep him out of the end zone. Whoever is responsible for McBride—whether it's Fred Warner, Dee Winters, Marques Sigle, Jason Pinnock, or Ji'Ayir Brown—must do a good job of limiting McBride's production.
Attack The Secondary
The Cardinals' secondary has been hit with the injury bug. They're also young and ranked 26th in passing, allowing 255.5 yards per game. Expect Brock Purdy or Mac Jones to push the ball down the field for explosive plays. This could be the first 49ers game with 300 passing yards. If they can execute down the field, they will be at the top of the NFC West, sitting at 3-0.
Sunday will not be a cakewalk game. This game gives early bragging rights in the NFC West. After being swept in 2024, there's no way the 49ers want to start 2025 by allowing the Cardinals to win three straight. If the 49ers stick to these keys to victory, they will snap the losing streak against Arizona and remain undefeated this season.