Jones-Drew, 27, has missed the last nine games because of a sprained left foot suffered Oct. 21. He gained 414 yards on 86 carries prior to the injury.
The Jaguars placed him on the injured reserve list Friday.
He led the NFL with 1,606 yards on 343 carries in 2011 and was coming off three consecutive seasons in which he had more than 1,300 yards and was selected to the Pro Bowl each year.
Jacksonville is 30th in the NFL in team rushing after finishing 12th in that category in 2011.
The Jaguars, tied at 2-13 with the Kansas City Chiefs for the worst record in the NFL, end their season Sunday at Tennessee.