The Patriots were bidding to become the first team to retain the title since they themselves achieved the feat in 2004 and 2005, but they were outscored in an extraordinary contest which saw a host of records broken.
Bill Belichick's side, who had reached their eighth Super Bowl in the Belichick-Tom Brady era, pulled off a stunning comeback in last year's showpiece and threatened to do the same again this time around when Brady - chasing a record sixth winning ring - led the Patriots down the field towards the end of the contest.
However, Brandon Graham produced the first and only sack of the entire game in timely fashion to halt their momentum, and a late Hail Mary attempt failed as the Eagles hung on to claim a stunning victory.
Philadelphia quarterback Nick Foles - appearing in his first Super Bowl - completed a remarkable rise towards the end of the campaign by leading the Eagles' offense to victory, having only been brought in for Carson Wentz three games before the end of the regular season.
The outstanding play saw the Eagles pull off a trick move during which tight end Trey Burton threw the ball to Foles in the endzone, making him the first player to ever throw and catch a touchdown in a Super Bowl.
Foles went on to be named the game's MVP with three touchdowns and 373 passing yards, despite his opposite number Brady throwing for 505 yards and also registering three touchdowns.
Ultimately it was Zach Ertz's score with less than three minutes remaining which proved to be the winning touchdown, although the Patriots fought until the death in search of their record-equalling sixth Super Bowl victory, and third in the last four years.
The two teams combined for 1,151 yards in total - the most ever seen in one NFL game, either regular or post-season - with the Patriots becoming the first team to put up more than 600 yards of offense in a match and still end up on the losing side.
Brady did add another record to his collection as his tally of Super Bowl touchdowns rose to 18, but ultimately he fell short of adding to his legacy in one of the most memorable Super Bowls in history.