Alex Rodriguez, Nick Swisher and Russell Martin also homered for the Yankees, who handed the Red Sox their fourth straight loss. Ivan Nova (3-0) got the win, allowing two runs on seven hits with five strikeouts over six innings.
Red Sox starter Clay Buchholz (1-1) went six-plus innings, giving up six runs on nine hits, including all five New York home runs.
The teams wore replica uniforms to observe the 100th anniversary of the oldest MLB ballpark currently in use. The first game at Fenway, April 20, 1912, featured the Red Sox against the New York Highlanders -- who went on to become the Yankees.
The anniversary celebration featured appearances by all surviving Red Sox uniformed players and managers, wearing jerseys from the eras in which they played or coached.