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Casey Stengel of the Detroit Tigers hit the first home run in Yankee Stadium (the house that Ruth built) as by definition, an in-the-park home run is a hit that sends a batter (with no fielding errors) from home plate, around the bases and back to home plate.
Jorge Posada was the first player to hit a home run in the new Yankee Stadium, completed in 2009.
Jorge Posada hit the first home run in Yankee Stadium II. Posada hit the home run in the 5th inning, off Cleveland Indians pitcher Cliff Lee over the center field wall on April 16, 2009.
Robinson Cano hit the first home run at the "new" Yankee Stadium in an exhibition game played against the Chicago Cubs on April 3, 2009.
George Herman "Babe" Ruth in the first game ever played in Yankee Stadium. Hence it's nick name (the House that Ruth Built)