The Angels' Vladimir Guerrero connected off Yankees starter Joba Chamberlain for the 216th home run hit this year in the Bronx, doing so in the new facility's 73rd game.
The previous record was 215 home runs, set across the street at the classic Yankee Stadium in 2004.
Nick Swisher followed Guerrero's second-inning homer with a solo shot off Jered Weaver to lead off the third inning.
The only seasons in which 200 homers were hit at the old Yankee Stadium were 2004, 2000 (209) and 2005 (206), according to STATS LLC.
Yankee Stadium topped the Majors in home runs entering play on Monday -- Rangers Ballpark was second, with 197. The Major League record for home runs hit in a single season at a ballpark was 303, at Denver's Coors Field in 1999.
Bryan Hoch is a reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.