Sproles was injured in the first half following an awkward plant and hit from safety Darian Thompson.
Sproles, 34, indicated earlier that he was considering retiring at the end of the season.
There is better news about defensive tackle Fletcher Cox (calf) and middle linebacker Jordan Hicks (ankle).
The two injuries ended Sproles' 2017 season, and put the future of his National Football League playing career very much in limbo. Blount matched Smallwood with 12 carries and had 67 yards.
Eagles head coach Doug Pederson will meet the media at 1 p.m. Monday at the NovaCare Complex when he will likely address Sproles' injuries.
Off the field, the Eagles will be losing one of the most respected players in the locker room. Sproles has yet to find the endzone this season and has seven catches for 73 yards to go with 12 rushes for 50 yards. Rookie Corey Clement and quarterback Carson Wentz each had six carries for 22 yards. After five seasons in San Diego, he played for the Saints for three years before signing with the Eagles ahead of the 2014 season.