Lee (10-7) surrendered four runs on eight hits in a 7 2/3-inning start, walking a pair as the Phillies clinched their three-game set with the Pirates and improved to 68-39, best in the major leagues.
Howard's solo shot in second inning broke a scoreless tie and put Philadelphia ahead for good. The first baseman made it 4-0 in the third with a two-run double.
Jimmy Rollins also went deep for the Phillies.
James McDonald (7-5) absorbed the loss, giving up five runs on 10 hits over five frames for the Pirates, who fell 3 1/2 games off the pace in the National League Central.
Pedro Alvarez socked a two-run homer and Neil Walker went 3-for-4 with an RBI for Pittsburgh.