Lee (6-2) logged his fourth victory in five starts, stymieing Boston on four hits while issuing no walks and striking out eight in a 95-pitch performance.
Former Boston closer Jonathan Papelbon pitched a scoreless ninth for his 10th save as the Phillies bounced back from a 9-3 loss in the first game of their home-and-home interleague set.
Erik Kratz sent home John Mayberry with an RBI single in the seventh, breaking a 1-1 tie.
Michael Young and Domonic Brown each homered in the victory.
Boston's Ryan Dempster (2-6) pitched well in the loss, yielding two runs on six hits over seven full frames.
Dustin Pedroia supplied the only RBI for the Red Sox.