Armstrong described his years of denial as "one big lie that I repeated a lot of times." He had races to win and a fairy tale image to keep up.
He reminisced on his storied past of being a hero who overcame cancer, winning the Tour repeatedly, having a happy marriage, children. "It's just this mythic, perfect story, and it isn't true," he said.
Former teammate: More needs to happen
Former cyclist Tyler Hamilton, who raced as a teammate of Armstrong from 1998 to 2001, said it was nice to hear Armstrong own up to some of his faults.
Hamilton was among those who broke from Armstrong and decried his use of performance-enhancing drugs. Armstrong at the time denied the allegations and threatened him with legal action.
"He's made the first step," Hamilton told CNN's Piers Morgan before the second interview aired. "There are many more steps to come for Lance Armstrong."
According to Hamilton, the next step for the disgraced cyclist is to testify before cycling officials about the doping network, naming names as needed.
The U.S. Anti-Doping Agency, which tests Olympic athletes for performance-enhancing drugs, similarly described the interview as a "small step in the right direction."
"If he is sincere in his desire to correct his past mistakes, he will testify under oath about the full extent of his doping activities," USADA CEO Travis Tygart said.
The International Cycling Union called it "disturbing" to see Armstrong's confessions, but it said the sport is much different today than it was 10 years ago.
"Lance Armstrong's decision finally to confront his past is an important step forward on the long road to repairing the damage that has been caused to cycling and to restoring confidence in the sport," union president Pat McQuaid said.
Years of success and defiance, then a rapid fall
After winning various legs of the Tour de France, Armstrong's sporting career ground to a halt in 1996, when he was diagnosed with cancer. He was 25.
He told Winfrey that he then developed a "ruthless and relentless" attitude that helped him survive. But he carried it with him into his sports career, "and that's bad," he said.
He returned to the cycling world, however. His breakthrough came in 1999, and he didn't stop as he reeled off seven straight wins in his sport's most prestigious race. Allegations of doping began during this time, as did Armstrong's vehement defiance.
He left the sport after his last win, in 2005, only to return to the tour in 2009.
Armstrong still insists he was clean when he finished third that year, but that comeback led to his downfall.
"We wouldn't be sitting here if I didn't come back," he told Winfrey.
In 2011, Armstrong retired once more from cycling. But his fight to maintain his clean reputation continued. Federal prosecutors launched a criminal investigation, but it was dropped in February.
In April, the USADA notified Armstrong of an investigation into new doping charges. In response, the cyclist accused the organization of trying to "dredge up discredited" allegations and filed a lawsuit in federal court trying to halt the case.
Those who suffered for speaking out now feel vindicated.
They include Betsy Andreu, wife of fellow cyclist Frankie Andreu, who said she overheard Armstrong acknowledge to a doctor treating him for cancer in 1996 that he had used performance-enhancing drugs.
"This was a guy who used to be my friend, who decimated me," Andreu told CNN's Anderson Cooper on Thursday night. "He could have come clean. He owed it to me. He owes it to the sport that he destroyed."
The former athletic icon conceded he'd let down many fans "who believed in me and supported me."
"I will spend the rest of my life ... trying to earn back trust and apologize to people."