With a full house cheering from the pregame player introductions, the Red Sox pounded 12 hits, three by Pedroia. They started the season on the road by going 0-6 for the first time since beginning the 1945 season at 0-8.
They had been a popular preseason choice to reach the World Series after adding Carl Crawford and Adrian Gonzalez to support what seemed like a strong rotation. But the struggles of the starters continued when John Lackey (1-1) gave up six runs in five innings.
He still got the win when Jarrod Saltalamacchia's run-scoring double broke a 6-6 tie in the fifth.
Jonathan Papelbon, coming off his worst season, got the save with a perfect ninth inning as Boston won its seventh straight home opener.
J.D. Drew had given him a three-run cushion with a two-run single in the seventh.
The game started poorly for the Red Sox as Lackey walked the first batter, Brett Gardner, who stole second. After a walk to Alex Rodriguez, Robinson Cano drove a two-run double to deep center field.
Boston also showed some pop early as Pedroia hit his first homer in the first, a solo shot just inside the left field foul pole.
The Yankees went ahead 3-1 in the second on doubles by Curtis Granderson and Gardner before the Red Sox scored five runs in the bottom of the inning. They hadn't score more than five in a game in any of their first six losses.
The runs came off Phil Hughes, who was hammered for his second straight outing and lasted just two innings.
Boston loaded the bases in the second on singles by Drew, Saltalamacchia and Jacoby Ellsbury and scored when Marco Scutaro grounded into a forceout at third. Then Pedroia drove in two runs with a single and Adrian Gonzalez and David Ortiz singled in a run apiece for a 6-3 lead.
Lackey kept struggling, giving up an RBI double to Cano in the third, a run-scoring single to Derek Jeter in the fourth and a homer to Rodriguez, his third of the season, in the fifth.
That tied the game at 6, but Boston went ahead in the bottom of the fifth against Bartolo Colon (0-1) on a double by Saltalamacchia that scored Kevin Youkilis, who had drawn his third walk.
The Red Sox won despite another terrible performance by Lackey.
In his first start, he allowed nine runs and 10 hits in 3 2/3 innings of a 12-5 loss at Texas. So far this season, he has allowed runs in eight of the nine innings in which he's appeared with 13 of the 17 hits he's allowed going for extra bases.
Notes
When asked before the game about Boston's 0-6 start, Yankees manager Joe Girardi noted he was with the 1998 Yankees who opened 1-4 and went on to a 114-48 record in the regular season and a World Series title. … Rodriguez's homer was his 616th and gave him 1,836 RBIs, passing Rafael Palmeiro and tying Ken Griffey Jr. for 13th place. … Carl Yastrzemski, who made his major league debut 50 years ago in a Red Sox uniform and went on to the Hall of Fame, threw out the ceremonial first pitch. … A pregame moment of silence was observed for Lou Gorman, Boston's general manager from 1984 to 1993 who died on April 1 at the age of 82. … Another moment of silence was held in honor of victims of the earthquake and tsunami in Japan.