Cardinals RB James Conner Carted Off After Gruesome Injury

The Arizona Cardinals' rushing woes just increased.

Sep 21, 2025; Santa Clara, California, USA; Arizona Cardinals running back James Conner (6) is tackled by San Francisco 49ers linebacker Dee Winters (53) during the first half at Levi's Stadium. Mandatory Credit: Cary Edmondson-Imagn Images | Cary Edmondson-Imagn Images

The Arizona Cardinals lost star running back James Conner in the third quarter of their Week 3 battle against the San Francisco 49ers.

He was quickly ruled out with an ankle injury after exiting action.

Conner, who was tackled on Arizona's opening drive to the second half, immediately began reaching for his leg - which drew immediate concern from everybody in the stadium.

OMG James Connor’s knee went the other way

Prayers up, this looked like an ACL or MCL tear 😢#AZvsSF pic.twitter.com/O9QQ46KrkU

— Benchwarmer Sports (@bdubsports_) September 21, 2025

He was then carted off. RB Trey Benson will take his place in Arizona's offense the rest of the way.

Conner left with 22 rushing yards on nine carries.

Conner is fresh off consecutive 1,000 yard rushing years for the Cardinals, which netted him a nice contract extension earlier in the year to remain in the desert.

Voted as a team captain, the loss of Conner will be felt heavily on and off the field.

Arizona is currently down 6-3 as of publish.

Conner has been a key part of Drew Petzing's offense, which has drawn heavy criticism after a slow start running the ball in 2025 - which has been a hot topic around Arizona.

“Two years ago, I think we were top five. I'm not sure what we were last year, but I think that is something that we definitely hang our hat on," Kyler Murray said earlier this week.

"Trying to win the line of scrimmage and being able to get the run game going, establish that. In the past two games (there’s been) kind of lack thereof but hats off to the other team. They've done a good job being stout in the run game, making us have to move the ball in other ways—which I think that we can do, and I think we're capable of. I think we've shown that, but at the same time, I think that's just something that's part of the game.

"You see how the game's going, you see how the flow of it is. Obviously, I think that's something that (Offensive Coordinator) Drew (Petzing) likes to get across, but we've been better in the past and I think that's something that we have to be better at going forward.”

This week, Cardinals head coach Jonathan Gannon also added, "(It) needs to be better. I do think that. Just our efficiency of it, and we played some premium players in there too for two weeks—and that’s not an excuse. It needs to be better, and playing penalty-free in the run game too has to be a little bit better because when you have runs that go for two or three yards, it’s like, ah.

"You wish you would’ve gained a little bit more and been a little more efficient, but when you foul and now it’s second-and-20 instead of second-and-seven, it’s a whole different game. I think just what we talked about, that’s a collective effort. Play with a little bit better technique, play with a little bit more awareness, some details, make sure we’re doing the right things and make sure we’re putting them in good spots.”

This article will be updated with any further information.