In his youth, Greene participated in both American football and athletics, but eventually proved to be best in the latter.
In 1995, Greene took part in his first major international tournament at the World Championships in Gothenburg, but was eliminated in the 100 m quarter-finals. His next season was disappointing, as he failed to make the American team for the 1996 Summer Olympics in Atlanta.
However, the following season would mean his breakthrough. At the World Championships in Athens, Greene won the 100 m title. This marked the beginning of a dominance of especially the 100 m by Greene, successfully defending his title in 1999 and 2001, winning the Olympic championships in Sydney 2000 and setting the world record at 9.79 (beating the July 1996 record of Donovan Bailey at 9.84). At the 1999 World Championships, he also won the 200 m title, the first to win both events at a World Championships.