"As he was getting ready to leave the building, everyone of the Harpo staff lined the hallway to shake his hand," Winfrey would later recall. "We now call that hallway the 'Nelson Mandela Hallway' here at Harpo." (Harpo is Winfrey's production company.)
"This has not happened before or after," she said.
Before Winfrey's staff lined up to meet the anti-apartheid leader who emerged from prison to become South Africa's first black president, Mandela discussed his heroic life and how, branded a terrorist and traitor by South Africa's apartheid government, he survived nearly 30 years in captivity.
"You must fight the battle for dignity on the very first day you go to jail and that's what we did. We put our foot down and insisted on being respected even though were prisoners," Mandela said.
Mandela spent much of his time in prison on Robben Island, where he was made to do forced labor and was permitted just one visitor a year; he could either write or receive one letter every six months. Despite those limits on communication, he completed a law degree, organized protests within the prison and helped lead the movement against apartheid.
"If I have not been to prison, I would not have been able to achieve the most difficult task in life and that is changing yourself," Mandela told Winfrey in 2000.
"I was in the company of great men," he said of his fellow prisoners. "Some of them were more qualified, more talented than I am, and to sit down with them to exchange views was one of the most revealing experiences I had."
In reflecting on how he held no bitterness towards his captors and went on to lead the country, Mandela said that thinking of his time in prison left him feeling "angry."
"Our emotions said the white minority is our enemy [and] we must never talk to them, but our brains said if you don't talk to this man, your country will go up in the flames. And for many years to come, this country would be in rivers of blood," Mandela said. "So we had to reconcile that conflict and our talking to the enemy was the result of the domination of the brain over emotions."
After developing a personal bond with Mandela, Winfrey went on to found the Oprah Winfrey Leadership Academy for Girls just outside Johannesburg, in Mandela's native country.
"To be in his presence is like being in the presence of grace and royalty at the same time," Winfrey said in introducing Mandela on her 2000 show. "It is one of the greatest honors of my career to welcome Nelson Mandela."
In 2011, when Winfrey ended her show, she named the Mandela interview as one of the top 17 headline-making moments in the show's 25-year history.
Upon hearing of Mandela's passing on Thursday, Oprah called Mandela her "hero" and said his life was "a gift to us all."
"One of the great honors of my life was to be invited to Nelson Mandela's home, spend private time and get to know him," Winfrey said in a statement. "He was everything you've ever heard and more - humble and unscathed by bitterness. And he always loved to tell a good joke. Being in his presence was like sitting with grace and majesty at the same time."