Harper took the first pitch he saw in the first inning from Colorado's Antonio Senzatela to dead center field Saturday.
The home run is the longest by a Phillies player at Citizens Bank Park since 2015. Ryan Howard hit a 505-foot homer at Citizens Bank Park in June 2007.
"It was pretty cool," Harper told reporters. "Of course I enjoyed it a little bit."
Harper raised his season average to .230 with two hits Saturday. He has eight home runs and 28 RBIs in 45 games this season.
Harper's home run had an exit velocity of 114.1 mph.
"Just as a fan, you stop and you watch the distance of the ball," Phillies manager Gabe Kapler said. "That's kind of rare territory. Pretty impressive."