Winfrey told the audience that she loved "The Oprah Winfrey Show," that it had been her life and that she knew when it was time to say goodbye. "Twenty-five years feels right in my bones and feels right in my spirit," she said.
Winfrey talked about being nervous when the program began in 1986 and thanked audiences who had invited her into their homes and lives over the past two decades.
"I certainly never could have imagined the yellow brick road of blessings that have led me to this moment," she said.
The powerhouse show became the foundation for her multibillion-dollar media empire but saw its ratings slip 7 percent last season before rebounding in the last couple months. Winfrey, 55, is widely expected to start up a new talk show on OWN: The Oprah Winfrey Network, a much-delayed 50-50 joint venture with Discovery Communications Inc. that is projected to debut in January 2011. OWN is to replace the Discovery Health Channel and will debut in some 80 million homes.
Winfrey offered no specifics about her plans for the future, except to say that she intended to produce the best possible shows during her last 18 months on the air.
"Over this holiday break, my team and I will be brainstorming new ways that we can entertain you and inform you and uplift you when we return here in January," she said. "And then, season 25 - we are going to knock your socks off."
CBS Television Distribution, which distributes the show to more than 200 U.S. markets, held out hope it could continue doing business with Winfrey, perhaps producing a new show out of its studios in Los Angeles.
"We know that anything she turns her hand to will be a great success," the CBS Corp. unit said in a statement. "We look forward to working with her for the next several years, and hopefully afterwards as well."
Many fans heading into Harpo Studios on Friday morning seemed to support Winfrey's decision.
"It's time to elevate to something new," said Sandra Donaldson, 59, of Indianapolis. "Whatever she does is going to be a blessing. It's going to be rewarding and eye-opening. Her name alone opens doors."
Once a local Chicago morning program, the production evolved into television's top-rated talk show for more than two decades, airing in 145 countries worldwide and watched by an estimated 42 million viewers a week in the U.S. alone.
Audience members described the atmosphere inside the studio Friday as tense and emotional, with some reaching for tissues as Winfrey announced her decision. But amid the sadness, there also was understanding among the crowd, Donaldson said afterward.
"When I looked around, there was a peace there, because I like to think everybody was happy for her decision to move on," she said.
Fans expressed hope that Winfrey would soon announce another project.
"Oprah, she impacts everybody, her life, the way she gives," said Shawana Fletcher, 29, of Chicago. "I hope she's not totally done. That's what we're praying."
Winfrey's 24th season opened this year with a bang, as she drew more than 20,000 fans to Chicago's Magnificent Mile for a block party with the Black Eyed Peas. She followed with a series of blockbuster interviews - Mike Tyson and Evander Holyfield, Whitney Houston and ESPN's Erin Andrews, and just this week, former Alaska governor and GOP vice presidential candidate Sarah Palin.
As a newcomer, "The Oprah Winfrey Show" chipped away at talk-show king Phil Donahue's dominance. Later, it turned to inspiration. The show's coverage ranged from interviews with the world's celebrities to an honest discussion about Winfrey's weight struggles.
In 1986, pianist-showman Liberace gave his final TV interview to Winfrey, just six weeks before he died. In a 1993 prime-time special, Michael Jackson revealed he suffered from a skin condition that produces depigmentation. Tom Cruise enthusiastically declared his affection for the much-younger Katie Holmes on the program in 2005 - and jumped on the couch to prove it.
In 2004, Winfrey unveiled her most famous giveaway, when nearly 300 members of the studio audience opened a gift box to find the keys to a new car inside. The stunt became a classic show moment as much for Winfrey's reaction - "You get a car! You get a car! You get a car! Everybody gets a car!" - as its $7 million price tag.
The show also became a launching pad for Oprah's Book Club, which then launched best-sellers. The titles ranged from "Song of Solomon" and "Paradise" by Toni Morrison to Wally Lamb's "She's Come Undone" and Elie Wiesel's "Night."
For others, the selection backfired. "A Million Little Pieces" exploded in sales after Winfrey chose the James Frey memoir in fall 2005. Soon after, it was revealed as a fabricated tale of addiction and recovery, and Winfrey later chewed out Frey on her show.
The loss of "The Oprah Winfrey Show" would be a blow to CBS Corp., which earns a percentage of hefty licensing fees from TV stations that use it - largely ABC affiliates. CBS Chief Executive Leslie Moonves told analysts two weeks ago that the contract with the show runs through most of 2011 and "if there's a negative impact, it wouldn't hit us until '12."
"Oprah's been a force of media and there's really no person you can look to out there who you could say, `That's the heir apparent,"' said Larry Gerbrandt, an analyst for Media Valuation Partners in Los Angeles. Gerbrandt noted many stations build their schedules around Winfrey's show.
"It's a big loss, but not as huge as it would have been 10 years ago," he said. "However, it still commands the biggest audience and ABC station competitors are licking their chops."
Talk of the show's end often has accompanied Winfrey's contract negotiations. Before signing her current contract in 2004, she talked about quitting after the 2005-2006 season. As far back as 1995, she called continuing "a difficult and important decision."
Winfrey started her broadcasting career in Nashville, Tenn., and Baltimore, Md., before relocating to Chicago in 1984 to host WLS-TV's morning talk show "A.M. Chicago" - which became "The Oprah Winfrey Show" one year later. She set up Harpo the following year and her talk show went into syndication.
Winfrey built a media empire powered by the show's success. Harpo Studios produces shows hosted by Dr. Phil McGraw and celebrity chef Rachael Ray. O, The Oprah Magazine was the nation's 7th most popular magazine in the first half of 2009.
Earlier this year, Forbes scored Winfrey's net worth at $2.7 billion.
In daytime, her show is head and shoulders above all other talk shows, with 6.8 million viewers on average in the last couple months, compared with "Dr. Phil" with 3.8 million, "Ellen" at 2.8 million and "Dr. Oz" with 3.5 million, according to The Nielsen Co.
Even with such a lead, her ratings have been falling over the years, with an average audience cut in half from 12.6 million in 1991-92 to 6.2 million in 2008-2009.
That decline in audience numbers argued for a move to cable where audiences are increasingly finding niche programming.
AP Business writers Ryan Nakashima in Los Angeles and Andrew Vanacore in New York contributed to this report.