The following is a list of the largest margins of defeat by a home team in its stadium opener in baseball history.

16 runs
April 18, 1991: Tigers 16, White Sox 0; Comiskey Park II

9 runs
March 31, 2003: Pirates 10, Reds 1; Great American Ballpark

8 runs
April 19, 1890: Chicago Pirates 10, Pittsburgh Burghers 2; Exposition Park III (debuted with Players League)
May 13, 1901: White Sox 11, Brewers 3; Lloyd Street Grounds
April 16, 2009: Indians 10, Yankees 2; Yankee Stadium

7 runs
April 6, 1977: Angels 7, Mariners 0; Kingdome
March 31, 1998: Rockies 9, Diamondbacks 2; Bank One Ballpark

6 runs
June 30, 1970: Braves 8, Reds 2; Riverfront Stadium
April 9, 2001: Reds 8, Pirates 2; PNC Park

5 runs
April 17, 1902: Cubs 6, Reds 1; Palace of the Fans
April 14, 1904: Athletics 8, Senators 3 (8 innings); American League Park II
April 21, 1910: Tigers 5, Indians 0; League Park II
April 15, 1977: Phillies 7, Expos 2; Olympic Stadium
March 31, 1998: Tigers 11, Devil Rays 6; Tropicana Field

Source: Retrosheet.org