While O'Reilly said she never saw Armstrong use banned substances -- though she felt sure that he did -- Hamilton had a different story, saying "the first time I ever blood-doped was with Lance" and that Armstrong was well aware and involved with everything that happened.
The Massachusetts-born cyclist recalled how the U.S. Postal Service team had a French man, whom he referred to as Motoman, who followed the tour on his motorcycle to deliver the performance-enhancing drug EPO at different stops.
Asked why few cyclists on his team were caught despite what he characterized as repeated doping, Hamilton said they just did as they were told.
"The team doctors told us what we could take, when we could take it, how long it would stay in our system," he said. "So if we followed those simple rules, 99 times out of 100, we would pass."
Having first tested positive for doping in 2004, Hamilton said he continued to lie -- pointing to what he called omerta, or "the code of silence ... within the top tier of cycling."
"I believed that was my only way back into the sport," he said. "It is a bit of a mafia. It's a powerful group. You can say the wrong thing, and next thing you know ..."
It wasn't until last year, with an interview on CBS' "60 Minutes" and the publication of a book the following year, that Hamilton came clean about being a chronic user.
He said telling the truth has been cathartic for him, while expressing understanding about his former teammate's continued denials.
"I lied for a long, long time. And you start believing some of your lies," said Hamilton, who accused Armstrong of trying to intimidate him a year and a half ago. "And he's got himself really backed into a corner."