Brown's three-run blast in the fifth inning was immediately followed by Mayberry's solo shot as the Phillies scored five time to break the contest open.
Rookie right-hander Jonathan Pettibone (1-0) collected his first major-league win, surrendering three runs on seven hits over five innings.
Mets starter Shaun Marcum (0-1) went four full innings in making his first start of the season following a stint on the disables list with a neck strain. He was touched for three runs on five hits.
John Buck cracked his eighth homer of the year for New York.