McCoy took a hard hit to his knee on a tackle by Redskins defensive back Dashon Goldson following an 8-yard reception and remained on the ground. McCoy later jogged to the sideline under his own power, tested his injury under the supervision of the medical staff and then departed for the locker room, shaking his teammates' hands on the way.
McCoy rushed 10 times for 29 yards before his injury. He was replaced by Mike Gillislee, who ran 60 yards for a touchdown later in the third quarter.
The Bills (6-8) will miss the postseason for the 16th year a row, the longest active drought in the NFL.