Nix (1-0) got off to a rocky start. He stranded three runners after a pair of singles and a walk in the first, and two more runners in the second. Then he settled down, allowing one more baserunner the rest of the game, retiring 11 of his last 13 batters faced and striking out four.
Freddy Galvis hit a two-out RBI single in the second to put the Padres up 1-0. Austin Hedges scored from second after initially reaching base on a bloop single, and then stealing second.
Hedges then added a solo homer on a 1-2 pitch in the fourth to put the Padres up 2-0. It was Hedges ninth home run of the season.
Down 2-0, the Phillies appeared to be threatening after a leadoff single and a walk to start the seventh inning, but Padres reliever Matt Strahm struck out the next two and induced a weak ground ball out to end the inning.
Strahm, Craig Stammen and Kirby Yates combined for three innings of scoreless relief.
Odubel Herrera and Maikel Franco both singled to lead off the ninth for the Phillies, but Yates struck out two of the last three batters to pick up his fourth save of the season after replacing former Padres closer Brad Hand.
Eric Hosmer had three hits, joining Galvis and Hedges as the only Padres to have hits.
Phillies starter Zach Eflin (8-4) gave up both runs and five hits over six innings. He struck out eight.
Padres: Rookie LHP Eric Lauer (left forearm strain) played long toss before the game without any reported issues.
Phillies: RHP Aaron Nola takes the mound against the Padres looking to bolster his Cy Young credentials.
Padres: RHP Walter Lockett looks to grab his first win of the season on Saturday night.