VIDEO: Farewell race, Tour DownUnder
The 39-year-old American, who made a comeback to the sport two years ago, said he was quitting for good to spend more time with his family and his charities.
"Today, I am announcing my retirement from professional cycling in order to devote myself full-time to my family, to the fight against cancer and to leading the foundation I established before I won my first Tour de France," he said in a statement.
Armstrong, who won a record seven Tour de France titles after surviving cancer, retired from cycling in 2005 but returned in 2009, finishing third in the Tour de France. His final race was at the Tour Down Under in Australia last month.
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