Ryan Howard knocked in two runs, Jimmy Rollins scored twice and Michael Young had three hits - two that never left the infield - for the second straight day. Pettibone (1-0) pitched his way out of an important jam to help Philadelphia improve to 4-1 against the Mets after losing the season series last year.
Shaun Marcum (0-1) went four innings in his Mets debut after beginning the season on the disabled list with a neck injury and right biceps tendinitis. John Buck hit his eighth homer in the ninth, way too late to prevent New York from dropping to 3-5 on a nine-game homestand with its third straight defeat.
Making his second start in place of injured John Lannan, Pettibone threw 96 pitches in five innings. But he limited the Mets to three runs on seven hits after holding Pittsburgh to a pair of solo homers over 5 1-3 innings Monday.
Pettibone's father, Jay, made four starts for the Minnesota Twins in 1983 and played for Phillies manager Charlie Manuel at Double-A Orlando a year later.
Philadelphia has won five in a row and nine of 12 at Citi Field, dating to 2011.
David Wright and Jordany Valdespin had RBI doubles for the Mets, who fielded the same shuffled lineup that was shut out by Kyle Kendrick on three singles Friday night.
Brown hit a three-run shot to right off reliever Rob Carson in the fifth and Mayberry drove the next pitch way out to left, making it 8-2. It was the second set of back-to-back homers for the Phillies this season, both against the Mets.
Pettibone loaded the bases with none out in the fourth on consecutive singles and a four-pitch walk. But after a mound visit from pitching coach Rich Dubee, the 22-year-old righty minimized the damage.
Ike Davis hit a sacrifice fly to the left-field warning track, Valdespin forced a runner at second and Pettibone threw a called third strike past pinch-hitter Justin Turner to preserve a 3-2 lead.
That was the end of the afternoon for Marcum, pulled for the pinch hitter, and Philadelphia immediately broke it open against a dreadful New York bullpen that began the day ranked next-to-last in the majors with a 5.02 ERA.
Rollins doubled off Carson to start the fifth and Howard was credited with an RBI single when his hard smash skipped right through Ruben Tejada's legs, eating up the shortstop with an in-between hop.
Brown and Mayberry followed with much longer shots off Carson, who retained his spot in the bullpen Saturday when New York demoted fellow left-hander Josh Edgin to make roster room for Marcum.
Philadelphia added an unearned run in the seventh against LaTroy Hawkins on an RBI single by Laynce Nix. Tejada robbed Mayberry of a run-scoring single with a diving grab.
Pettibone helped himself at the plate, too. He sparked Philadelphia's three-run third with a leadoff single for his first major league hit and scored on Chase Utley's ground-rule double. Rollins dashed home on Marcum's wild pitch and Howard added a sacrifice fly.
Howard has 21 RBIs in his last 12 games against the Mets.