Armstrong, while maintaining his innocence, made his decision after a US federal court dismissed his lawsuit against USADA, paving the way for the agency to continue its probe into the retired American cyclist.
Armstrong accused USADA of launching a "witch hunt" against him and said they were playing with a loaded deck.
"Today I turn the page," Armstrong said in a statement on his Twitter website yesterday evening. "I will no longer address the issue, regardless of the circumstances. I will commit myself to the work I began before ever winning a single Tour de France title."
The 40-year-old said he was growing weary of the fight and the strain it had put on his personal and professional life.
Lance Armstrong. Photo: AFP
"There comes a point in every man's life when he has to say 'enough is enough.'
For me, that time is now," Armstrong said. "The toll this has taken on my family and my work for our foundation and on me leads me to where I am today -- finished with this nonsense."
Armstrong's decision to stop fighting USADA means he could be stripped of his seven Tour de France titles he won from 1999-2005. His decision could also lead to a lifetime ban from cycling.
USADA says Armstrong used banned substances, including the blood-booster EPO and steroids, as well as blood transfusions dating back to 1986. Armstrong, who retired from cycling last year, sued in federal court to try and halt USADA's probe but lost.
"The bottom line is I played by the rules that were put in place by the UCI, WADA and USADA when I raced," Armstrong wrote.
"The idea that athletes can be convicted today without positive A and B samples, under the same rules and procedures that apply to athletes with positive tests, perverts the system and creates a process where any begrudged ex-teammate can open a USADA case out of spite or for personal gain or a cheating cyclist can cut a sweetheart deal for themselves.
"It's an unfair approach, applied selectively, in opposition to all the rules. It's just not right."