During his nine-year stint in the Major Leagues, Greene played for four different teams: the Cincinnati Reds (1992–1998), the Baltimore Orioles (1998), Toronto Blue Jays (1999), and finally the Chicago Cubs (2000).

Greene was the Pittsburgh Pirates' first pick in the 1989 June draft, and was also Georgia's Gatorade Player of The Year in baseball (1989). He was traded to the Montreal Expos on August 8 of 1990 with Scott Ruskin and Moisés Alou for Zane Smith.