The Oprah Winfrey Show will end its run in 2011 after 25 seasons on the air, Winfrey's production company said.
Winfrey plans to announce the final date for her show during a live broadcast today, Harpo Productions Inc said.
The broadcast that grew over two decades into a daytime television powerhouse and the foundation of a multibillion-dollar media empire.
It will bring an end to what has been 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 US alone.
A Harpo spokeswoman declined to comment on Winfrey's future plans except to say that The Oprah Winfrey Show will not be transferred to cable television.
Winfrey is widely expected to start up a new talk show on the Oprah Winfrey Network, a much-delayed joint venture with Discovery Communications Inc that is expected to debut in 2011.
OWN is to replace the Discovery Health Channel and will debut in some 74 million homes.
Winfrey's 24th season opened earlier this year with a bang, as she drew more than 20,000 fans to the city's Magnificent Mile on Michigan Avenue for a Chicago block party with the Black Eyed Peas.
Powered by the show's staggering success, Winfrey built a wide-ranging media empire.
Harpo Studios produces shows hosted by Dr Phil McGraw and celebrity chef Rachael Ray. Her "book club" selections produce instant best-sellers and O, The Oprah Magazine was the nation's seventh most popular magazine in the first half of 2009.
"I came from nothing," Winfrey wrote in the 1998 book Journey to Beloved.
"No power. No money. Not even my thoughts were my own. I had no free will. No voice. Now, I have the freedom, power, and will to speak to millions every day - having come from nowhere."
Earlier this year, Forbes rated Winfrey's fortune at 2.7 billion US dollars, even as the magazine knocked her from the top of its list of the world's most powerful celebrities.
The honour went to Angelina Jolie, but Winfrey was still number two on the annual Celebrity 100 list.
Winfrey followed up the block party this year with a series of blockbuster interviews - Mike Tyson and Evander Holyfield, an exclusive with singer Whitney Houston and just this week, former Alaska governor, vice presidential candidate and best-selling author Sarah Palin.
She found time between shows to lobby the International Olympic Committee in Denmark for Chicago's failed bid to host the 2016 Olympics.
Winfrey started her broadcasting career as a teenager in Nashville, Tennessee, reading the news at WVOL.
Two years later, Winfrey started co-anchoring news broadcasts on WTVF-TV in Nashville. In 1976 she moved to Baltimore to anchor newscasts at WJZ-TV before becoming host of the local talk show People Are Talking.
In 1984, she relocated to Chicago to host WLS-TV's morning talk show A.M. Chicago - the show became The Oprah Winfrey Show one year later.