Sparked by the return of Manny Ramirez, Trot Nixon and Jason Varitek, the Red Sox tied the score in the ninth inning and beat the Chicago White Sox 3-2 Monday night on Pena's home run leading off the 10th.
"Do you know how many times I'm doing this in my backyard? It's amazing," said Pena, who grew up about 40 miles north of Boston and went to college at Northeastern. "It's definitely the most exciting moment of my career, no doubt about it."
Boston, which won for just the third time in 10 games, trailed 2-1 in the ninth when Ramirez walked on four pitches leading off against Bobby Jenks. He moved to second on Nixon's groundout to first, then scored on Mike Lowell's double into the left-field corner. It was just the third blown save in 42 chances for Jenks.
Pena's homer, his first since last Oct. 2, was a drive into the right-field seats on a 2-1 pitch from Brandon McCarthy (3-6).
"He threw a bad pitch to the wrong guy," Chicago manager Ozzie Guillen said. "This guy's got a lot of power and he hit it out of the ballpark."
With the loss, Chicago gave up the AL wild-card lead and fell a half-game behind Minnesota. The Red Sox, who trail the Twins by six games, won despite scoring three runs or fewer for the 13th time in 15 games.
"I don't think we're tight," McCarthy said. "But we're not playing up to our full potential. We did this last year. I don't think you can make a defending World Series team tight."
Pena, released by the Yankees Aug. 15 and signed by the Red Sox two days later, was called up from Triple-A Pawtucket on Aug. 28.
Mike Timlin (6-4) pitched a hitless inning for the victory.
Chicago returned to Fenway Park for the first time since eliminating the Red Sox in last year's playoffs, and starter Jon Garland left in position to get what would have been his major-league leading 17th win. He gave up one run and five hits in six innings.
Julian Tavarez, starting for Boston because Curt Schilling has a mild strain on his right side, gave up two runs and six hits in 6 1/3 innings. Bouncing off the mound on nearly every grounder and pointing to first excitedly as his fielders made plays, he got 14 outs on grounders.
"It looked like he was having a ball out there, throwing strikes," Boston manager Terry Francona said.
Tavarez held the White Sox to four singles before Jim Thome tied the score in the seventh with his 38th homer, a drive into the seats above the Green Monster.
Tavarez was just happy to get the opportunity to start for Boston's depleted staff. Jon Lester was diagnosed with a form of lymphoma one day after David Wells was traded to San Diego. Tim Wakefield is also sidelined with a fractured rib.
"They might give me another chance," Tavarez said.
Paul Konerko doubled to chase Tavarez and first baseman Kevin Youkilis kept the game tied with a diving stop on A.J. Pierzynski's grounder, but Joe Crede blooped a single to center off Manny Delcarman to give Chicago a 2-1 lead.
Garland retired 13 straight batters after loading the bases in the first before Youkilis and Mark Loretta singled to open the sixth. Eric Hinske grounded into a double play but, after Ramirez was intentionally walked, Nixon hit a soft liner just over the glove of second baseman Tadahito Iguchi for an RBI single.
- Jermaine Dye left the game in the seventh with tightness in his back.
- Francona on the possibility of Schilling taking his next turn in the rotation: "I don't think he looks very encouraging."
- Red Sox CF Coco Crisp was rested due to a sore left shoulder.
- Boston recalled LHP Javier Lopez from Triple-A Pawtucket.
- The Red Sox hung a banner on the Green Monster before the game, honoring Schilling's accomplishment as the 14th pitcher to reach 3,000 strikeouts.
- Chicago LF Scott Podsednik was 1-for-17 before a sixth-inning bunt single.
- Tavarez made his longest outing since he pitched seven innings for Florida against Pittsburgh on Aug. 30, 2002.