Armstrong, 41, has always vehemently denied using the drugs and had never tested positive in a doping test. But the evidence against him has been overwhelming and pressure has been building on him to admit that he cheated.
USA Today reported on Monday that Armstrong had confessed to the doping in the interview with Winfrey, which will air on Thursday and Friday on her OWN Network, and other media say they have confirmed the report.
In an appearance on CBS' "This Morning" show on Tuesday, Winfrey did not explicitly say that Armstrong had confessed during their interview, though she said the media had confirmed it.
"I think the most important questions and answers that people around the world have been waiting to hear were answered," Winfrey said of the interview, which occurred at a hotel in Austin, Texas, and lasted more than two hours.
"We were mesmerized and riveted by some of his answers," said Winfrey, who described Armstrong's demeanour as thoughtful and serious and at times emotional.
When asked why the American cyclist, who had his seven Tour de France titles stripped last year, agreed to the interview, Winfrey said: "I think he was just ready." She added that she would allow others to decide if he had shown contrition.
A cancer survivor who went on to become the greatest cyclist the world has seen, Armstrong's fall from grace has been as swift and spectacular as his rise through the French Alps.
While Armstrong was long dogged by accusations he cheated his way to the top, his rapid slide was ultimately triggered by an October report from the U.S. anti-doping body USADA.
USADA exposed Armstrong as a liar and a cheat, describing him as the ringmaster of the "most sophisticated, professionalized and successful doping program that sport has ever seen," involving anabolic steroids, human growth hormone, blood transfusions and other doping.
Media reports of the interview with Winfrey have not identified which drugs he reportedly admitted using. Armstrong's attorney and his spokesman did not immediately respond to requests for comment on the reports on Monday.
Armstrong, however, apologized on Monday to the staff of the cancer foundation he started over difficulties they may have experienced because of the doping controversy.
"It was a very sincere and heartfelt expression of regret over any stress that they've suffered over the course of the last few years as a result of the media attention," Livestrong Foundation spokeswoman Katherine McLane said on Monday.
CBS has reported that Armstrong indicated he might be willing to testify against others involved in illegal doping and was in talks about repaying part of the taxpayer money he earned during his career.
Former Armstrong teammates at his U.S. Postal and Discovery Channel outfits, where he won his seven successive Tour de France titles from 1999 to 2005, testified against him as well as admitting to their own wrongdoing.
The mountain of evidence was overwhelming, and when Armstrong decided not to fight the charges against him, his Tour de France victories were quickly nullified. He was banned from cycling for life.
His sponsors, who had remained loyal to him, began deserting him and he stood down as chairman of Livestrong. Legal issues began to mount.
His former team-mate Floyd Landis, a self-confessed cheat, filed a lawsuit against him for defrauding the U.S. government, while the London-based Sunday Times is suing Armstrong to recover about $500,000 it paid him to settle a libel lawsuit.
Armstrong could also be forced to pay back amounts including $7.5 million to SCA Promotions, a Dallas-based company that paid him a bonus for his Tour de France wins.
Throughout it all, Armstrong remained silent, unrepentant and seemingly unconcerned as the cycling world was left reeling by the revelations. He agreed last week to the interview with Winfrey.