A tearful Oprah Winfrey has announced her talk show will end in September 2011 after 25 years on the air.
Speaking to her live studio audience, the chat show queen said she had decided to end the show "after much prayer and months of careful thought".
"I love this show, and I love it enough to know when it's time to say goodbye," the 55-year-old said.
Winfrey's show, currently syndicated in 145 countries, has transformed the star into a cultural phenomenon.
"Twenty-five years feels right in my bones, and it feels right in my spirit - it's the perfect number, the exact right time," she said.
Winfrey also promised she would be working with her production team to find new ways to entertain, inform and uplift her audience for her remaining shows.
"We are going to knock your socks off. And until that day in 2011 when it ends, I intend to soak up every meaningful, joyful moment with you," she said.
The Oprah Winfrey Show's open atmosphere and frank conversation redefined the talk show genre and made Winfrey one of the most influential women in the US as well as the wealthiest black woman in the world.
Her reputation was clearly appreciated by the big-name stars who opened their souls on her show, from Michael Jackson to Tom Cruise - who famously jumped on the sofa to announce his love for his future wife Katie Holmes.
The introduction of Oprah's Book Club helped authors whose novels were selected become bestsellers overnight, and Winfrey's support for US President Barack Obama was seen as crucial to his presidential election campaign.
Winfrey's empire also includes magazines, books and a satellite radio station - Oprah Radio - with presenters including Dr Maya Angelou and sex therapist Dr Laura Berman.
She is expected to focus instead on the launch of her own cable TV network in 2011.
OWN: The Oprah Winfrey Network is a joint venture between Winfrey and Discovery Communications and is set to replace the Discovery Health Channel in more than 70 million US homes.
Oprah is still the highest-rated US talk show with an average seven million daily viewers, but audiences are half what they were a decade ago.
Winfrey's announcement comes less than 24 hours after Tim Bennett, president of Winfrey's Harpo production company, broke the news to TV stations that broadcast the show.
In a letter he wrote: "The sun will set on the Oprah show as its 25th season draws to a close on 9 September 2011."
The end of the programme will be a blow to distributor CBS, which earns a percentage of licensing fees - estimated to be worth hundreds of millions of dollars - from the more than 200 local ABC TV stations across the US that broadcast it.
Many stations also built their schedules around Winfrey's show, using it to promote other programmes while also delivering a large audience to their local news programming.