For the hundreds of network affiliates who depended on Winfrey to deliver millions of viewers every day, Friday's announcement starts an 18-month clock to find a way to fill the space left behind after the end of the most successful daytime talk show in television history.
Winfrey's show "is one of daytime television's very foundations," said Larry Gerbrandt, an analyst for the firm Media Valuation Partners in Los Angeles. "You could, and stations did, build their schedules around her. They gave it the best time period, leading into their news, and used it to promote other shows."
Winfrey cautioned viewers that they would hear "a lot of speculation in the press about why I am making this decision," warning them not to listen to the "conjecture." But she offered no specifics about her plans for the future, except to say that she intended to produce the best possible shows during the final two years.
"I just wanted to say whether you've been here with me from the beginning or you came on board last week, I want you all to know that my relationship with you is one that I hold very dear," she said. "Your trust in me, the sharing of your precious time every day with me has brought me the greatest joy I have ever known."
It has also brought her a fortune estimated at $2.7 billion. As a newcomer, she chipped away at the dominance of Phil Donahue. She flirted with a tabloid format for a time, but gradually reinvented her show to focus on themes of inspiration, hope and the power of positive thinking.
"She's made such an imprint in today's society. She's just part of everyone's lives," said Yasmeen Elhaj, a 19-year-old student from Chicago who was in the studio for Friday's announcement. "People talk about Oprah like that's her friend. So that's why everyone is sad to see her go because she's just a giving person, feels like she's your home girl."
The show has a breadth that no other has been able to match. A serious hour on domestic abuse could be followed the next day by a rollicking party with the Black Eyed Peas.
When Whitney Houston and Sarah Palin wanted to talk this fall, Winfrey's show was their first stop. An endorsement by Winfrey for her book club is a make-or-break opportunity for authors.
But even Winfrey was not immune to the dips in ratings that have plagued broadcasters as viewers flock to specialty programming on cable. Her average audience - easily the largest of daytime talk shows - fell from 12.6 million in 1991-92 to 6.2 million in 2008-2009.
This season, boosted by blockbuster interviews with Palin, Houston and others, the show is doing better, averaging 7.2 million viewers a day.
The decline in audience numbers has long argued for a move to cable, where audiences are increasingly able to finding niche programming.
Winfrey, 55, is widely expected to start up a new talk show on OWN: The Oprah Winfrey Network, a joint venture with Discovery Communications Inc. that was first announced last year. It will replace the Discovery Health Channel and debut in some 80 million homes.
Discovery is pouring resources into OWN to prepare for its January 2011 launch. Chief Financial Officer Brad Singer told analysts this month that Discovery plans to invest $30 million to $40 million in 2009 on programming, staffing and other costs.
Discovery also is lending the venture $100 million, and OWN hired "Oprah" co-executive producer Lisa Erspamer this month as its chief creative officer. Erspamer is expected to move from Chicago to Los Angeles in January.
Winfrey's move to cable leaves a gap in the afternoon programming at many TV stations, where it leads into the local evening news and is popular with advertisers. At the peak of her ratings in the 1990s, Oprah could almost single-handedly prop up the newscast on WFAA-TV in Dallas, an ABC affiliate, because her fans stayed with the station, said Mike Devlin, the station's president and general manager.
"I hate to see her go. I'm an Oprah fan," Devlin said. "But all things end."
There are other syndicated shows available - "Live with Regis and Kelly," "The Ellen DeGeneres Show," "Rachael Ray Show," "Dr. Phil" and "The Tyra Show" - but none has the reach or influence of "Oprah."
And it's not easy to come up with a winning formula. Magic Johnson, Megan Mullally, Queen Latifah, Tony Danza, Lauren Hutton, Sinbad and Keenen Ivory Wayans are just some of the people who have tried to launch talk shows with abysmal results.
"There's always cycles in the television business," said Emily Barr, the president and general manager at WLS-TV in Chicago. "We are thrilled to have had this long association with Oprah and we will miss her, but we will also move on and see what else is out there."
Nakashima reported from Los Angeles. Associated Press writers David Bauder and Andrew Vanacore in New York contributed to this report.