In a program taped a day earlier at Oprah's Harpo Studios in Chicago, Winfrey took to the stage and, in what has become almost a mantra over a quarter-century, urged her audience to follow their dreams.
"Start embracing the life that is calling you and use that life to serve the world,"
As the show drew to a close, Winfrey became emotional, a few tears escaping as she looked back on what she would call her "life's journey."
An estimated 40 million Americans watched her show each week, which is distributed in 150 countries. And she is not disappearing from TV screens, as she will now turn to running her own network, OWN.
Thanks to her business savvy, Winfrey is today one of the world's richest women, heading a multimedia entertainment conglomerate, with ventures in theater and Hollywood film.
She also is a massive force in the book publishing industry thanks to her on-air book club.
She even had an influence in politics, famously risking alienating part of her viewership by endorsing then-candidate Barack Obama in the last presidential election.