At age 16, Armstrong began competing as a triathlete and was a national sprint-course triathlon champion in 1989 and 1990. In 1992, he began his career as a professional cyclist with the Motorola team. Armstrong had success between 1993 and 1996 with the World Championship in 1993, the Clásica de San Sebastián in 1995, Tour DuPont in 1995 and 1996, and a handful of stage victories in Europe, including stage 8 of the 1993 Tour de France and stage 18 of the 1995 Tour de France. In 1996, he was diagnosed with a potentially fatal metastatic testicular cancer. After recovering, Armstrong founded the Lance Armstrong Foundation (now the Livestrong Foundation) to assist other cancer survivors.

Returning to cycling in 1998, Armstrong was a member of the US Postal/Discovery team between 1998 and 2005 when he won his seven Tour de France titles. Armstrong retired from racing at the end of the 2005 Tour de France, but returned to competitive cycling with the Astana team in January 2009, finishing third in the 2009 Tour de France later that year. Between 2010 and 2011, he raced with Team Radio Shack and retired for a second time in 2011.