It took years of defiant rejection of his critics, recovery from cancer, seven now-discredited Tour de France victories and a position at the heart of the "most sophisticated doping programme sport has ever seen".
Winfrey has confirmed that Armstrong, who in October was stripped of all his titles and labelled a "serial drug cheat" by the United States Anti-Doping Agency (Usada), will seek redemption on her show.
In a 90-minute interview from his home in Austin, Texas, he will speak publicly for the first time about the doping revelations that led to a lifetime ban from sport. It will be streamed live around the world on Oprah.com next Thursday as well as broadcast in the US at 2am UK time.
It is the first time Armstrong has given an interview since he lost his titles, was dropped by sponsors and pilloried by the public for his part in a doping conspiracy that spanned more than a decade and was described in excoriating detail in a 202-page report by Usada.
Within hours, bookmakers were offering odds on which words Armstrong would use in the interview, with Ladbrokes quoting 1-4 on "apologise" and evens on "confess". They were offering 8-11 on Armstrong breaking down in tears.
Travis Tygart, the Usada chief executive, told the Guardian in an interview last month that he hoped an Armstrong confession could yet act as a powerful symbol for drug-free sport.
But others, including another former cycling drug cheat who has since become a respected anti-doping campaigner, immediately voiced concerns that a stage-managed talkshow was not the right forum to discuss claims that as recently as October Armstrong's lawyer was dismissing as a "one-sided hatchet job".
"Only Lance would get to have his moment of truth, if that's what it will be, in front of Oprah Winfrey," said British cyclist David Millar, who was banned for two years in 2004 for injecting EPO at a time when doping was rife in the professional peloton.
"It is not sitting in front of a judge or a disciplinary hearing being properly questioned about the things he has done wrong. I doubt very much it will be a proper interrogation," added Millar, who is a member of the World Anti-Doping Agency's athletes commission. "My biggest concern is that it will be completely stage-managed, that he will just be 'given the ball', and that it will all be about his emotions rather that concentrating on exactly what he did wrong."
A spokeswoman for the Oprah show said Armstrong was not being paid to appear and that Winfrey was free to ask any question she wanted. "No payment for the interview. No editorial control, no question is off limits," the spokeswoman said in an email.
The Oprah Winfrey Network (OWN), which will show the programme, is a joint venture between Winfrey's Harpo Productions and Discovery Channel. Discovery was the headline sponsor of Armstrong's team between 2004 and 2007.
It was that network's logo that was emblazoned on his shirt when he won his seventh Tour in 2005 and claimed it as a victory over "the people that don't believe in cycling, the cynics and the sceptics". Discovery was a vocal supporter of Armstrong and one of the last sponsors to distance itself from the Texan once Usada's damning evidence was published.
Former colleagues and rivals immediately began speculating on whether Armstrong would use the programme as a platform for contrition or an attempt to shift the blame. Armstrong had previously told a US tribunal that he had never used performance-enhancing drugs, opening up the possibility that he could perjure himself if he now admitted doping.
The Texan is at the centre of several ongoing legal disputes, while the Sunday Times is suing him for the repayment of a libel settlement the newspaper was forced to pay him over doping allegations.
Many fear Winfrey will give Armstrong an easy ride, recalling her interview with Olympic gold medallist Marion Jones, in which the weeping American sprinter claimed she took performance-enhancing drugs unintentionally.
Kathy LeMond, wife of the US Tour de France winner Greg, tweeted: "@Oprah I hope you get educated before the interview. I know people that can help you."
Since Usada published its "reasoned decision" in October, ratified some weeks later by cycling's much criticised global governing body, the UCI, Armstrong has been deserted by a succession of high-profile supporters and sponsors, including Nike, and lost millions of pounds' worth of endorsements. He has also stepped down from his position as chairman of Livestrong, the charity he established to help fellow sufferers after winning his battle with testicular cancer.
Reports in the US at the weekend suggested he was considering making a confession and wanted to negotiate with the World Anti-Doping Agency over his ability to compete in the field of triathlon and running events.
guardian.co.uk © Guardian News and Media Limited 2010
image: © bike