Tua Tagovailoa was injured with 4:24 remaining in the third quarter.
The Dolphins quarterback scrambled up the middle on fourth-and-four at the Buffalo 13 and as he got past the first down line, he lowered his head. His head jammed into Bills defensive back Damar Hamlin.
At the same time, his right leg stuck underneath him.
He went directly into the locker room, walking under his own power with a limp.
Tagovailoa did not miss a game in 2023, but he had a series of concussions in 2022 that had him consider retirement.
The Dolphins announced that Tagovailoa is out with a concussion.
Skylar Thompson is in at quarterback for the Dolphins, who trail 31-10.
Tagovailoa is 17-of-25 for 145 yards with a touchdown and three interceptions.
The Dolphins also have lost two offensive linemen, with Terron Armstead (shoulder) and Robert Jones (shoulder) both questionable to return.