The world-renowned talk show host did not back down in any soft approach in getting to the bottom of one of world sport's most controversial issues of the past decade.
After a week of speculation whether she would ask the most crucial question - whether Armstrong was a drug cheat - she did not back down.
Winfrey got right to the point, asking for yes-or-no answers to five questions.
Did Armstrong use banned substances? "Yes."
Did he use EPO? "Yes."
Did he do blood doping and transfusions? "Yes."
Did he use testosterone, cortisone and human growth hormone? "Yes."
Did he do it in all seven of his Tour wins? "Yes."
The disgraced former cycling champion acknowledged what he had lied about repeatedly for years, and what had been one of the worst-kept secrets for the better part of a week: He was the ringleader of an elaborate doping scheme on a US Postal Service team that swept him to the top of the podium at the Tour de France time after time.
"At the time it did not feel wrong?" Winfrey asked.
"No," Armstrong replied. "Scary."
"Did you feel bad about it?" she pressed him.
"No," he said. "Even scarier."
"Did you feel in any way that you were cheating?"
"No," Armstrong paused. "Scariest."
"I went and looked up the definition of cheat," he added a moment later.
"And the definition is to gain an advantage on a rival or foe. I didn't view it that way. I viewed it as a level playing field."
- With AAP