The teams met up the next day for Game 2, which matched the accomplished Curt Schilling against 23-year-old, nineteen game winner Fausto Carmona. Schilling got into some early trouble, when Grady Sizemore and Victor Martinez doubled, giving the Indians a quick 1-0 lead. The Sox went down quickly in the bottom of the inning, although David Ortiz did reach on a walk, keeping his reputation as an impossible out intact.

Both pitchers went quickly through the second, but in the third, the heart of the Red Sox order was back up at the plate. With Coco Crisp and Dustin Pedroia aboard, Big Papi singled, reaching base in his tenth straight plate appearance. That loaded the bases for Manny Ramirez. He walked, forcing in a run, just like he had done twice in Game 1. Mike Lowell followed with a big single, driving in two more runs for a 3-1 Red Sox lead. Unfortunately, Schilling gave the three runs right back, on a three-run homer by Jhonny Peralta in the top of the fourth. It got worse in the fifth, when Sizemore homered for a 5-3 Indians lead. Two more singles knocked Schilling from the game, with Manny Delcarmen coming in to retire the side. When Kevin Youkilis singled to lead off the home half of the fifth, that was the end of the night for Carmona. The rest of the game would be pitched by the bullpens, and, if the regular season was any indication, Boston had a decided edge in that department.

Big Papi followed Youkilis's single with a fielder's choice to second, the first out he made in the series. But it was followed by Manny Ramirez's 23rd career postseason home run, an all-time record, and it tied the game 5-5. Lowell followed with his own home run, and the Sox were back on top 6-5. It was now up to the best bullpen in the league to hold the lead. But Delcarmen struggled in the sixth, and the Indians turned a walk, a single, and a groundout into the tying run. Hideki Okajima finished the sixth and pitched a 1-2-3 seventh, and Mike Timlin took care of a scoreless eighth. With the game still tied, it was Jonathan Papelbon's turn in the ninth. The Sox got pinch-runner Jacoby Ellsbury to second with two outs in the bottom of the ninth, but Youkilis couldn't knock him in, and the game went into extra innings.

Papelbon came back out for the tenth and retired the side in order. But in the eleventh, it was up to Eric Gagne. He got one out, but then the trouble started. Sizemore singled and Asdrubal Cabrera walked. Left-handed Trot Nixon came in to pinch-hit. Nixon was a former Red Sox fan favorite who always played hard and had had some big postseason hits. But he never had much success against lefties, so southpaw Javier Lopez was called in to face him. Trot wasn't a starter anymore, but he showed his new team that he could still come up with a big hit. He singled into center, knocking in the go-ahead run for the Indians. Before anyone knew what had happened, the whole inning unraveled. Lopez threw a wild pitch, scoring another run. He issued an intentional walk, then gave up another RBI hit. That was it for Lopez, who couldn't even record an out, and Jon Lester was in. Ideally, Lester never would have been called upon in the middle of an inning, since he was the team's fifth starter who was assigned to the bullpen for the playoffs but had never pitched in relief. But there was no alternative at that point, and Lester was greeted with an RBI double. He managed one out, but then Franklin Gutierrez launched a three-run homer, making the score a suddenly ugly 13-6. The seven-run inning by the Indians was the largest offensive output in an extra inning in postseason history, and it helped Cleveland even the series at one game apiece.