The Miami Dolphins running back will miss their finale Sunday against the New York Jets. He was ruled out by coach Todd Bowles after missing practice for the third consecutive day Friday.
Bush, a 1,000-yard rusher this year for the first time in his six-year career, hurt his right knee late in last week's loss at New England.
Bush's absence Sunday likely means more work for rookie Daniel Thomas, although he has been nursing a knee injury too. The game is meaningless for the Dolphins (5-10), but the Jets (8-7) still have a shot at the playoffs.
After five years with New Orleans, Bush joined the Dolphins this season intent on showing he could handle the role of an every-down running back, and he did just that. He leads Miami with 1,086 yards rushing, many coming on dashes between the tackles.
His 216 carries were easily a career high, and he also made 43 catches for 296 yards. His seven touchdowns led the team.
"I already knew all the tools were there," the former Heisman Trophy winner said Thursday. "It was just about the opportunity. I had that opportunity coming here and tried to make the most of it."
Bush's average of 5.0 yards per rush is the highest for a 1,000-yard runner this year. He came on strong after an unimpressive first month of the season, and led the NFL with 519 yards rushing in December.