BOSTON (AP) -It was three hours into the game, and Mike Lowell was 0-for-3 with two strikeouts while stranding five baserunners.

The next two at-bats changed everything.

The former World Series MVP hit a three-run homer in the seventh to give the Red Sox the lead, then added a three-run double in the eighth in Boston's 16-11 victory over the New York Yankees . It was Boston's ninth straight win, and its biggest comeback victory against the Yankees since 1968.

''It was going back-and-forth; it seemed like whoever was up last was going to win,'' Lowell said. ''You've got to be mentally prepared for every pitch.''

In all, 12 pitchers threw 385 pitches and managed to retire the side in order just twice - once for each team - in a 4 hour, 21 minute game that tied for the sixth-longest nine-inning game in baseball history. The two longest also were between the Yankees and Red Sox .

''Lot of pitching changes. Lot of runs. Lot of commercials,'' Red Sox manager Terry Francona said. ''There's that many pitches thrown, and it seems like every one is of consequence. It can drain you.''

Boston was trailing 6-0 before Jason Bay singled in a run and Jason Varitek hit a grand slam to make it 6-5 in the fourth. The Yankees led 10-9 in the seventh when they intentionally walked Bay - Friday night's star - to face Lowell, and he homered off Jonathan Albaladejo (1-1) to make it 12-10.

The Yankees again walked Bay to get to Lowell in the eighth, and he drove in another three runs with a double off the Green Monster.

''His RBIs in the last few innings were the difference in the game,'' Yankees manager Joe Girardi said. ''In the first couple of at-bats, we weren't able to get Bay out. That combination has really hurt us in this series so far.''

Hideki Okajima (1-0) got two outs for the win, then Ramon Ramirez got out of the eighth after putting runners on second and third with one out. Dustin Pedroia had three hits and Jacoby Ellsbury hit his first homer of the year for Boston.

Robinson Cano homered twice and drove in five for the Yankees.

Yankees star Jorge Posada was called for catcher's interference and a passed ball in the same inning; Pedroia - the 2008 AL MVP - had a two-run error and got thrown out on a baserunning bungle. The teams swapped leads four times in fifth, sixth and seventh innings as Johnny Damon tied it with a two-run homer, David Ortiz hit a sacrifice fly put Boston on top and then the Yankees took the lead when Damon hit a hard grounder through Pedroia's legs at second base.

The Yankees intentionally walked Bay, whose two-run homer with two out in the ninth helped Boston win the night before. Lowell homered off Albaladejo inside the foul pole to make it 12-10.

The Red Sox last rallied from six runs down to beat the Yankees on May 16, 1968, when they trailed 9-3 after four innings but came back to win 11-10.

''They never quit over there,'' Damon said. ''Score a run here, score a run there, and then Varitek hits a big grand slam. Then they ended scoring every inning after that.''

Notes: Jamaican sprinter Usain Bolt, wearing a Red Sox jersey with No. 9.69 on the back for his record time in the 100 meters, threw out the ceremonial first pitch. ... Boston ace Josh Beckett and New York's A.J. Burnett, teammates on the 2003 World Champion Florida Marlins , were the starters and neither made it past five innings after giving up eight runs for a no-decision. ... Cano has hit safely in 12 straight games. ... New York's Mark Teixeira walked five times, once intentionally.