Bradford took what appeared to be a light hit from Cleveland defensive lineman Armonty Bryant as he threw incomplete for tight end Jared Cook. Bradford shrugged Bryant off but Bryant made contact with Bradford's surgically repaired left knee.
After a beat, Bradford fell to the ground in pain as Rams doctors and trainers rushed to his side. Bradford limped off the field under his own power but favoring the left leg. He went to the locker room for further examination.
A few plays earlier, Bradford escaped pressure from Cleveland linebacker Barkevious Mingo but took another hit on the knee.
Bradford was making his second start of the preseason after returning from a torn left ACL suffered against Carolina on Oct. 20, 2013 that ended his season.
Bradford went 4 of 9 for 77 yards before leaving. Veteran Shaun Hill entered to replace Bradford.
Information from The Associated Press was used in this report.