Hamels (6-1) gave up three runs on six hits while striking out nine and walking one. It was the sixth straight win for Hamels, who improved to 4-0 in five career starts against Boston.
Streaking Carlos Ruiz went 2 for 3 with a pair of RBIs for Philadelphia, which moved two games above .500 for the first time this season. Ruiz, who entered leading major league catchers in several offensive categories, is 11 for 17 in his last five games.
Jonathan Papelbon pitched a scoreless ninth for his 12th save in as many chances. Papelbon had 219 saves in six seasons with the Red Sox before signing a four-year, $50 million deal with Philadelphia in the offseason.
Adrian Gonzalez, Mike Aviles and Cody Ross homered for the Red Sox.
The game matched clubs with the second- (Phillies, $175 million) and third-highest (Red Sox, $173 million) payrolls, though each entered in last place in their division.
Daniel Bard (3-5), converted to a starter before this season, matched his shortest outing of the year by allowing five runs on three hits with five walks in five innings.
The right-hander struggled with control in the first inning when the Phillies scored four runs on just two hits thanks to three walks. Philadelphia went up 2-0 on Ruiz's two-run single to center before Ty Wigginton's sacrifice fly and John Mayberry Jr.'s RBI double gave the Phillies a four-run lead.
Boston got a run back in the third on Aviles' solo homer to left in the third. The Red Sox put runners on first and second with no outs in the fourth, but managed just one run on Daniel Nava's sacrifice fly.
Pence upped Philadelphia's advantage to 5-2 with a solo homer to left-center in the fifth before Ross responded with his own homer in the sixth to pull Boston within 5-3. It was Ross' fifth off of Hamels in 37 at-bats.
Gonzalez's homer off the second deck in right off reliever Chad Qualls in the eighth made it 5-4. But Galvis got the run back in the bottom of the frame with a solo shot to left off Franklin Morales.
Red Sox catcher Jarrod Saltalamacchia was forced to leave the game in the bottom of the fifth with a cut on his left ear after Bard's pitch hit Wigginton, deflected off Wigginton's right forearm and hit the catcher on the left side of the head just below the ear.
Saltalamacchia immediately went to the ground, appearing to be in a great deal of pain, and stayed face down for a few minutes before being attended to by the Boston training staff. He walked off under his own power and was replaced by Kelly Shoppach.
Boston manager Bobby Valentine was ejected in the ninth inning by first-base umpire Gary Darling for arguing Darling's out call at first base on Marlon Byrd's groundout.
Notes: Phillies manager Charlie Manuel missed the game after being suspended one game for his ejection by umpire Bob Davidson Tuesday night. ... Philadelphia's crowd of 45,205 was the 223rd straight sellout, and 239th counting postseason play. ... Former Red Sox manager Butch Hobson, now heading the Lancaster Barnstormers in the Atlantic League, became the 20th manager to reach 1,500 career victories with the club's win Thursday. ... Boston left-hander Jon Lester (2-3, 3.71) is scheduled to face Phillies right-hander Joe Blanton (4-3, 2.96) on Saturday night.
