Guice left at the end of the first quarter of Washington's preseason opener Thursday night against the Patriots after he was tackled following a 34-yard gain that was negated by a penalty.
Guice was selected in the second round of the 2018 NFL Draft out of LSU.
While the Redskins have been rotating their running backs in training camp, coaches have been pleased with Guice's development, and teammates anticipated him being the opening-game starter.
Brady, the reigning NFL MVP, is signed through the 2019 season.
The news is also a significant blow to Guice - and the latest knee injury to slow down his football career.
Kelley has earned praise from Jay Gruden, and Perine is said to be looking better than he did last season, when he averaged 3.4 yards per carry and didn't factor much into the receiving game.
Chris Thompson tweeted that he "had a tough time (trying to) hold back the tears" when he learned about the injury. Now, it's wide open after Guice's season-ending injury. "So, control what you can control".
Samaje Perine: "Bounce back bout to be insane!"
The team said tight end Manasseh Garner, a long shot to make the roster, is out for the season with an ACL injury.