The rocker sang Take Me Out to the Ball Game during the seventh inning stretch as the Cubs won their first World Series game at home to extend the baseball series against the visiting Cleveland Indians.
The Cubs went on to win 3-2 and the World Series will now head to Ohio for Game 6 on Tuesday (01Nov16).
Vedder, who also paid tribute to retiring Cubs star David Ross before launching into the sports anthem, wasn't the only celebrity Cubs fan watching history - die-hard Bill Murray was also spotted cheering on his team, while Chicago, Illinois sports nut John Cusack was also at the game.
Murray fulfilled his dream of singing Take Me Out to the Ball Game at a World Series game on Friday (28Oct16) at Wrigley Field.
Murray's enthusiasm bubbled over as he gave a rousing speech before he began to sing the song, which he bizarrely performed in the style of the Looney Tunes animated character Daffy Duck.
"It's the bottom of the 7th inning, the last chance to order beer. But we didn't come here to drink beer; we came here to win this ballgame," Murray yelled to the Wrigley crowd.
"In order to sing the right lyric - Take me out to the crowd - you need to sing it like our greatest American entertainer, Mr. Daffy Duck. So I want you to spray it and don't say it," he added.
"Let's get some runs, suckers," Murray shouted after the song ended.