Kramer became the sixth commissioner of the Southeastern Conference on January 10, 1990. Within seven months of his appointment, the conference announced plans for expansion, adding Arkansas and South Carolina officially on July 1, 1991. Following expansion, Kramer guided the conference in formulating divisional play and the first Division I-A conference football championship game.
During his tenure at the helm of the SEC, the conference won 81 national championships, the most ever in a decade by the league. Kramer oversaw the distribution of a then-league record $95.7 million to its member institutions for 2001–02. Kramer negotiated multi-sport national television packages with CBS and ESPN, featuring football and men's and women's basketball, through the 2008–09 season.
Because of his influence, the Men's and Women's SEC Athlete of the year award is presented annually as the Roy F. Kramer Award.
Kramer was succeeded as the SEC's commissioner by Michael Slive, who currently holds the position.