Armstrong walked away from the sport for good in 2011 without being charged following a two-year federal criminal investigation into many of the same accusations he faces from USADA.
The federal probe was closed in February, but USADA announced in June it had evidence Armstrong used banned substances and methods — and encouraged their use by teammates. The agency also said it had blood tests from 2009 and 2010 that were "fully consistent" with blood doping.
Included in USADA's evidence were emails written by Armstrong's former U.S. Postal Service teammate Floyd Landis, who was stripped of his 2006 Tour de France title after a positive drug test. Landis' emails to a USA Cycling official detailed allegations of a complex doping program on the team.
USADA also said it had 10 former Armstrong teammates ready to testify against him. Other than suggesting they include Landis and Tyler Hamilton, both of whom have admitted to doping offenses, the agency has refused to say who they are or specifically what they would say.
USADA maintains that Armstrong used banned substances as far back as 1996, including the blood-booster EPO and steroids, as well as blood transfusions.
"There is zero physical evidence to support (the) outlandish and heinous claims," Armstrong said. "The only physical evidence here is the hundreds of (doping) controls I have passed with flying colors."
Armstrong sued USADA in Austin, Texas, where he lives, in an attempt to block the case and was supported by the UCI. A judge threw out the case on Monday, siding with USADA despite questioning the agency's pursuit of Armstrong in his retirement.
"USADA's conduct raises serious questions about whether its real interest in charging Armstrong is to combat doping, or if it is acting according to less noble motives," such as politics or publicity, U.S. District Judge Sam Sparks wrote.
The ultra-competitive Armstrong still had the option to press his innocence in arbitration, which would have included a hearing during which evidence against him would have been presented. But the cyclist has said he believes most people have already made up their minds about whether he's a fraud or a persecuted hero.
And so he did something virtually unthinkable for him: He quit before a fight was over, a stunning move for an athlete who built his reputation on not only beating cancer, but forcing himself through grueling offseason workouts no one else could match, then crushing his rivals in the Alps and the Pyrenees.
"Today I turn the page. I will no longer address this issue, regardless of the circumstances," he said. "I will commit myself to the work I began before ever winning a single Tour de France title: serving people and families affected by cancer, especially those in underserved communities."
Although he had already been crowned a world champion and won individual stages at the Tour de France, Armstrong was still relatively unknown in the U.S. until he won the epic race for the first time in 1999. It was the ultimate comeback tale: When diagnosed with cancer, doctors had given him less than a 50 percent chance of survival before surgery and brutal cycles of chemotherapy saved his life.
Armstrong's riveting victories, his work for cancer awareness and his gossip-page romances with rocker Sheryl Crow, fashion designer Tory Burch and actress Kate Hudson made him a figure who transcended sports.
His dominance of the Tour de France elevated the sport's popularity in the U.S. to unprecedented levels. His story and success helped sell millions of the "Livestrong" plastic yellow wrist bracelets, and enabled him to enlist lawmakers and global policymakers to promote cancer awareness and research. His Lance Armstrong Foundation has raised nearly $500 million since its founding in 1997.
Jeffery C. Gervey, chairman of the foundation, issued a statement of support.
"Faced with a biased process whose outcome seems predetermined, Lance chose to put his family and his foundation first," Gervey said. "The leadership of the Lance Armstrong Foundation remain incredibly proud of our founder's achievements, both on and off the bike."