On July 29, 2016, Sproles signed a one-year $4.5 million contract extension with the Eagles through 2017. Sproles was an immediate weapon out of the backfield, catching 10 passes for 160 yards and a touchdown in the first three games of the season, however he was also held to only 51 yards on 19 carries rushing in that same timespan. In a Week 8 loss to the Dallas Cowboys, Sproles took over as the lead back, carrying the ball 15 times for 86 yards and catching 5 passes for 17 yards. Sproles would retain the lead back role the following week against the New York Giants, rushing 13 times for 57 yards, catching 3 passes for 14 yards, and gaining 76 yards on 2 punt returns. On November 7, the day after the Giants game, head coach Doug Pederson officially named Sproles as the starting back. Overall, he finished the 2016 season with 438 rushing yards, two rushing touchdowns, 52 receptions, 427 receiving yards, and two receiving touchdowns.