The Eagles later placed Sproles on injured reserve.
Sproles, 34, went down in the first half on an awkward play in which he suffered both a non-contact injury to his knee and a hard hit to his arm from Giants safety Darian Thompson. He walked off the field on his own power but was slated for an MRI on Monday to determine the extent of his injuries.
Wendell Smallwood, LeGarrette Blount and Corey Clement all received carries with Sproles out of the lineup and should continue to do so moving forward.
Sproles had 15 carries for 61 yards and seven receptions for 73 yards through the first three games. A free agent after the 2017 season, Sproles' next decision may be determining whether to continue his NFL career.
While still generally effective but with the same wear-and-tear running backs his age usually have, Sproles will be 35 next June and coming off major knee surgery. He previously told Tim McManus of ESPN that he was leaning toward retiring after the 2017 season.
However, it's possible Sproles will attempt to play in 2018 to go out on the field rather than on injured reserve.