The rookie suffered a torn ACL during Thursday's preseason game, NFL Network Insider Ian Rapoport reported, according to a source informed on the injury.
The team later announced the injury would wipe out the second-round pick's rookie season.
The initial diagnosis heading into Friday's MRI was that Guice had suffered only an MCL sprain. Alas, further tests proved much more damaging.
Guice exited Thursday night's tilt versus the New England Patriots after gaining 19 yards on six rushing attempts. The tailback injured his knee on a 34-yard scamper that was negated by a holding penalty.
The 21-year-old expressed confidence after the game, telling JP Finlay of NBC Sports Washington "all is well."
All was not well.
Guice's injury is a big blow to the Redskins backfield. The powerful rookie was expected to be an early-down thumper and complement to pass-catching back Chris Thompson. After just one preseason game, Washington is back to the drawing board.
With the rookie done for the year, Samaje Perine and Rob Kelly will battle for early-down duties. The Redskins also have Kapri Bibbs, Byron Marshall and undrafted rookie Martez Carter on the backfield depth chart.