The 2008 season was the last season played at historic Yankee Stadium, after which the team will move to New Yankee Stadium, which is located in Macombs Dam Park, adjacent to and north of the current field. Because of this, the 2008 Major League Baseball All-Star Game was played there on July 15, 2008.

The final regular season game at Yankee Stadium was played on September 21, 2008 against the Baltimore Orioles, the city from which both the Yankees and their great star Babe Ruth originated. Led by home runs from Johnny Damon and Jose Molina, the Yankees won 7–3. Molina's home run, a two-run shot hit to left-center field with one out in the bottom of the 4th inning, turned out to be the final home run in Stadium history. The final run was scored by Yankee pinch-runner Brett Gardner in the bottom of the 7th inning, and the final batter was Baltimore's Brian Roberts, who hit a ground-ball out to Yankee first baseman Cody Ransom, closing out 83 years of baseball history.