The deal makes Barkley the NFL's first $20 million-plus per-year running back.
Barkley, 28, also has the ability to earn an additional $15 million in incentives and escalators. The deal includes $36 million fully guaranteed at signing.
The extension comes after Barkley completed the first year of a three-year contract he signed with the Eagles in free agency last offseason.
Saquon Barkley hops off the bus and greets fans along parade route
In his first season with the Eagles, Barkley eclipsed Terrell Davis for most rushing yards in a single season in NFL history.
After rushing for 2,005 yards in the regular season, he rushed for another 499 yards in the postseason to finish with 2,504 total rushing yards.