Game 7 began at 8:30 in the evening on Wednesday, October 20, 2004 at Yankee Stadium. The starting pitchers were Derek Lowe for the Red Sox and Kevin Brown for the Yankees. Johnny Damon led off the game with a single to left and a stolen base, but was thrown out at home trying to score on a Manny Ramirez base hit. The very next pitch, however, was lined into the right-field bleachers by David Ortiz to give Boston a 2–0 advantage. In the second inning, the Sox loaded the bases against Brown, causing Yankees manager Joe Torre to remove him and put in Javier Vázquez to face Johnny Damon. Damon hammered Vázquez' first pitch into the right-field seats for a grand slam. The rout was on. Damon, who also added an upper deck two-run blast in the fourth, had three hits in the game, despite having only three hits previously in the series. Boston also enjoyed a solid performance from their starting pitcher, Derek Lowe, who allowed only one run and one hit in six innings of work. Lowe, who had significant bullpen experience for the Red Sox, was never even intended to be a starter in the postseason. He pitched game seven on just two days of rest.

Pedro Martínez relieved Lowe in the seventh inning, receiving loud chants of "Who's Your Daddy?," which intensified as he gave up a sequence of hits, allowing two runs. He eventually raised the velocity of his fastball to the mid-90s and shut down the rally. Mike Timlin and Alan Embree finished out the game. At 12:01 am, on October 21, Rubén Sierra hit a groundball to second baseman pokey Reese, who threw to first baseman Doug Mientkiewicz to finish the unprecedented comeback. The Red Sox won 10–3 and became the third team in sports history and the first since the 75 Islanders to win a seven-game series after losing the first three games. David Ortiz was named the series MVP.