Stanton started the fireworks in the top of the seventh, when he took New York starter Steven Matz (7-4) deep with Marcel Ozuna on first to give the Fish a 2-1 lead.
That was the only blemish on the night for Matz, as the lefty finished with six strikeouts and one walk over seven innings.
But Matz was outduelled by Wei-Yin Chen (5-3), who was perhaps overshadowed by Stanton’s performance.
A Yoenis Cepsedes solo shot in the fourth was the only damage that Chen gave up on the night (Cespedes came into the game slashing .333/.383/.560 in 75 at-bats against the Fish).
Chen made quick work of the Mets for most of the game. It took him only 87 pitches to record five strikeouts and only one walk over his seven innings of three-hit ball. His toughest inning came in the bottom of seven, when a Cespedes walk and James Loney single gave the Mets runners on first and second. With two outs, Juan Lagares lined a shot into right field, but Stanton bailed out his starter with a sliding catch to escape the inning without any damage.
Stanton added some insurance shortly thereafter, as he cranked a three-run shot to the second deck against reliever Erik Goeddel in the top of the eighth.
Fernando Rodney gave up a solo shot to pinch-hitter Alejandro De Aza in the bottom half, but that’s as close as the Mets would come as A.J. Ramos closed out his 25th save on the night he was named an All-Star reserve.
Rodney, Ozuna, and Jose Fernandez will be joining Ramos in San Diego as reserves.
Jose Reyes went 0-4 in his first game of the season, and his first game with the Mets since he signed with the Marlins in 2012.
The teams will wrap up their series with an afternoon battle on Wednesday.
Hero of the Game: Giancarlo Stanton (.565 WPA)
Goat of the Game: Erik Goeddel (-.245)
Play of the Game: Stanton's seventh-inning homer off Steven Matz (.364)