With the Nationals down to their final out and trailing 3-2 on Saturday night, Soto crushed the first pitch he saw from Phillies closer Hector Neris to left-center field. The ball traveled a projected 420 feet and silenced the Phillies crowd.
"He hung it and he threw it right down the middle," said Soto, who won't turn 21 until October. "For me, I just made an adjustment. I stepped to the front of the box, to hit in the front part of the box, and was just looking for that one. Maybe that's why I saw it a bit more hanging, and just hit it."
Veteran closer Sean Doolittle shut the Phillies down in the ninth to seal a 4-3 Nationals victory.
Saturday's home run was Soto's latest key hit against the Phillies. He hit a go-ahead three-run shot in the 10th inning of a 10-6 victory at Citizens Bank Park on April 9. Soto also had a go-ahead solo home run against the Phillies on Sept. 11, 2018.
Soto has a .327 average with nine home runs and 26 RBIs in 26 career games against the Phillies.
"I can't say enough about him," manager Dave Martinez said. "Being 20, and doing the things that he does, constantly wanting to learn more and more every day; I'm just glad that he's on our team. I really am."
Soto is hitting .302 with 16 home runs and 59 RBIs in 81 games this season.
Washington is 49-42 this season. The Nationals have a two-game lead over the Milwaukee Brewers for the National League's first Wild Card spot.