Thompson first appeared on the international scene as a 14-year-old in 1987, when she won the 50-meter freestyle and placed third in the 100 free at the Pan American Games. She won her first world championship in 1991, as part of the USA's winning 4x100 free relay team, and held the world record in the 50 and 100 free when she participated in the 1992 Olympics in Barcelona, Spain.
Thought to be at the height of her competitive career at the time, Thompson was expected to win up to five gold medals at those Olympics. However, she failed to qualify for the final in the 50 free, and finished second in the 100, where she was beaten by a Chinese swimmer who failed a test for steroids a year later. Although Thompson won two gold medals as part of the 4x100 free and 4x100 medley teams, she was angry about being beaten by the Chinese, whom she suspected of steroid use, and her comments on the issue raised considerable controversy.
Thompson continued her career as a part of the U.S. team and a member of the Stanford University team, and continued to rank among the world's best swimmers for the next four years. However, a poor performance at the 1996 Olympic Trials kept her from competing in any individual event at that year's Games in Atlanta. She redeemed herself there with three more relay golds, in the 4x100 free and medley and the 4x200 free.
Between 1997 and 1999, Thompson won eight more world championship titles, including three in a row in the 100 free, and went to the 2000 Olympics in Sydney, Australia hoping to finally win that elusive individual gold medal. It wasn't meant to be; she won a bronze in the 100 free and was fifth in the 100 butterfly. But in the relay events, she was super as usual--swmming the anchor leg in helping the USA defend its titles in the 4x100 free and medley and the 4x200 free. The 4x100 free and medley teams set new world records in the process.
At the World Championships that year, she broke the world record in the 100 butterfly for the fourth time, winning a qualifying heat in a time of 56.56 en route to a gold medal in the event.
Thompson seemingly retired from competition after the 2000 season with 10 Olympic medals, eight gold, one silver and one bronze, and 12 gold medals at World Championships. However, she returned to competition the summer of 2002 at the Pan Pacific Swimming Championships in Yokohama, Japan. Thompson won five medals in two days, setting a career-best time in winning the 50 freestyle.
Thompson was the 1993 and 1998 USA Swimming Swimmer of the Year. She ranked as the 62nd greatest female athlete of all time in a 1999 poll conducted by Sports Illustrated.