Lions coach Matt Patricia said earlier Monday he had briefly talked with doctors but would not know anything for sure until later on.
Johnson has been Detroit's lead back this season, rushing 92 times for 308 yards and two touchdowns. He injured the knee in the first half and did not return.
Shortly after the injury, he reappeared on the sideline in the second quarter with a brace on the knee and was riding the stationary bicycle behind the bench. He seemed to try and test the knee on the sideline after that, but did not come out of the locker room with the team after halftime.
He missed the last six games of last season with a left-knee injury after rushing for 641 yards.
With Johnson out, the Lions will look to a combination of rookie Ty Johnson and veteran J.D. McKissic to replace him. It's also possible Detroit could pursue a trade -- both as a replacement while Johnson is out and also as insurance when he returns.