It was Mahomes' opposing quarterback Jalen Hurts who started strongly with a one-yard rushing touchdown just a few minutes into the first quarter at State Farm Stadium in Glendale, Arizona.
Tight end Travis Kelce responded minutes later by scooping up a Mahomes pass to keep the scores level at 7-7.
Hurts had another impressive showing at the start of the second quarter, with the 24-year-old taking his side ahead on just the first play when he connected with wide receiver AJ Brown on a 45-yarder.
But that score was effectively cancelled on the next drive when Hurts fumbled while scrambling away from pressure, the ball then being picked up by Chiefs linebacker Nick Bolton who raced 36 yards to make it 14-14.
Hurts hit back later in the quarter with a 12-play, 75-yard drive that ended with him scoring from a four-yard run.
Unfortunately Mahomes' ongoing ankle injury featured, with Chiefs fans on edge when he limped away from a tackle during a three-yard run late in the second quarter.
Their fears eased, however, when he came on after Rihanna's halftime show and scrambled 14 yards to set up running back Isiah Pacheco's one-yard touchdown run that pulled the deficit back to 24-21.
Jake Elliott kicked another three points for Philadelphia just before the end of the third quarter, but the following quarter belonged almost entirely to Mahomes.
The 27-year-old, who was afterward awarded Super Bowl MVP for the second time, took his team ahead 35-27 with scoring throws to receivers Kadarius Toney and Skyy Moore, before Hurts levelled the scores with a two-yard rushing touchdown that he followed with a successful two-point conversion attempt.
But Kansas City kicker Harrison Butker had the final say with eight seconds left on the clock, when the Georgia Tech product capped Mahomes' 12-play, 66-yard drive with a successful 27-yard field goal for his side's second Lombardi trophy since 2019.