The 2001 Major League Baseball All-Star Game was the 72nd playing of the midsummer classic between the all-stars of the American League (AL) and National League (NL), the two leagues comprising Major League Baseball. The game was held on July 10, 2001 at Safeco Field in Seattle, Washington, home of the Seattle Mariners of the American League. The American League defeated the National League, 4–1. This was Cal Ripken, Jr.'s 19th and final All-Star Game. It was also the final All-Star Game for San Diego Padres legendary right fielder Tony Gwynn.

In the first inning, Alex Rodriguez elected to switch to third base so Cal Ripken, Jr. could play his original shortstop position, which the crowd applauded. The move allowed Ripken to set the record for most MLB All-star appearances at shortstop (15). Seattle's own Ichiro Suzuki gave his hometown fans something to cheer for early, when in the first, he singled off starter (and former Mariner) Randy Johnson, and then stole second. Randy Johnson stranded him at second to hold the AL scoreless in the first inning. Ripken followed this with a solo home run in the third inning, which also got a standing ovation, to put the AL up 1–0.

The AL scored one more run in the fifth when Iván Rodríguez singled home Jason Giambi to make it 2–0. Ryan Klesko hit a sacrifice fly to cut the lead to one in the sixth, scoring Jeff Kent from third. In the sixth, with the score 2–1, Derek Jeter and Magglio Ordóñez hit back to back home runs off Jon Lieber to extend the AL's lead to 4–1.

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