Daniel Murphy recorded three hits, an RBI and a run scored, while Chris Young knocked in a run and scored twice in support of Niese (2-2), who struck out five and scattered four hits with a walk over his solid start.
Niese helped his own cause with a bases-loaded walk in the fourth, as the Mets secured their second straight victory and fifth in their last six games.
Philadelphia starter Cole Hamels (0-2) had a forgettable outing, surrendering six runs on eight hits with five walks in just 4 2/3 frames. Hamels, who was making his first start of the season at Citizens Bank Park after starting the campaign on the disabled list, threw just 55 of his 106 pitches for strikes.
Marlon Byrd belted a solo homer to account for the lone run for the Phillies, who had a two-game win streak halted.