It was the Steelers' second loss in the pre-season in three matches, with Ben Roethlisberger unable to drive them to victory in Philadelphia.
Roethlisberger completed 15 of 24 passes, gaining 157 yards for one touchdown and one interception pass.
Meanwhile, Bruce Gradkowski made the most of his chance directing traffic for Pittsburgh, throwing two final-quarter touchdown passes, gaining 105 yards from eight completed passes.
Eagles playmaker Nick Foles gained 179 yards, as he completed 19 of 29 pass attempts for one touchdown pass and an intercept.
Matthew Tucker rushed for two touchdowns, gaining 46 yards on 10 attempts, while Darren Sproles also got into the end zone.
Steelers running backs Le'Veon Bell and LeGarrette Blount both played, one day after being arrested for marijuana possession.
The result was the Eagles' first victory of the pre-season, after losses to the Chicago Bears and the New England Patriots.