Penny went down in obvious pain after gaining 16 yards on a screen pass. He was initially ruled questionable to return before being downgraded to out.
"We don't know how serious it is, but it's significant," Seattle coach Pete Carroll said after the game.
Penny had started to come on of late. After spending most of his first season and a half playing sparingly behind Chris Carson, the 2018 first-round pick saw an uptick in his usage the past two games, playing a combined 65 offensive snaps to Carson's 70.
He had the most productive game of his career two weeks ago with 129 yards and a touchdown against Philadelphia, then scored twice last week against Minnesota. His 14 and 15 carries in those games were career highs.
Carson, meanwhile, entered Sunday night's game needing only 19 rushing yards to reach 1,000 for the second straight season, which he surpassed in the first half. He's the first Seahawks player with consecutive 1,000-yard rushing seasons since Marshawn Lynch in 2013 and '14.
Carson finished Sunday's game with 76 yards rushing on 15 carries, and he also caught three passes for 15 yards.
Penny's tweet and the way teammates talked about his injury had an ominous tone.
GOD makes no mistakes. Love you 12s . Thank you for the support💙💚— Rashaad Penny (@pennyhendrixx) December 9, 2019
"Well obviously it's disappointing losing Penny," Seahawks quarterback Russell Wilson said. "I feel for him. He's such a great competitor. He's been tremendous the past several weeks, so that's just unfortunate. It's part of the game unfortunately. I got to talk to him afterward and he had his head up, he's looking forward to where he's going next and just fighting through the rehab of it all and we'll be right there with him, but yeah, it was tough when you lose one of your key players -- a guy that you love to play with like Penny. He's been playing good football, too, for us, but Chris did well tonight. He made some key runs. Made some nice plays, some nice catches and stuff like that, so I thought Chris played well."
C.J. Prosise and rookie Travis Homer are the other tailbacks on Seattle's 53-man roster. Prosise has been injured for much of his career and has regularly been a healthy scratch this season while playing in only seven of Seattle's 13 games. He carried one time for 2 yards Sunday night. Homer has taken over kickoff return duties for Tyler Lockett and got his first and only career carry last week on a fake punt.
Carson and Penny are close friends. After the Seahawks' win last week, Penny lauded Carson for the selflessness he showed by taking himself out of the game after a long run that got the Seahawks to the goal line and set up one of Penny's two touchdowns.
"To be honest, I wasn't even thinking about it," Carson said of his 1,000-yard feat. "A couple players came up and congratulated me, but on a night like this, you lose one of your close friends, you don't get the win, I don't really pay too much [attention to it]."