She was born to a teenage mother in poor rural Mississippi, raised initially by her housemaid grandmother, and raped by a teenage cousin when she was nine.
From the age of 14, she finally found safety and stability with her father in Nashville.
Getting a break on a radio programme, Oprah Winfrey rose to become the darling of American talk shows, a best-selling author, the first African-American billionaire in the US, a cultural icon and household name, and one of the world's most influential women.
And after her speech last week at the Golden Globe Awards, many think she should make a run for the presidency in 2020.
"For too long, women have not been heard, or believed if they dared to speak their truth to the power of those men, but their time is up," she said at the awards ceremony.
"I want all the girls watching here, now, to know that a new day is on the horizon. And when that new day finally dawns, it will be because of a lot of magnificent women, many of whom are right here in this room tonight, and some pretty phenomenal men, fighting hard to make sure that they become the leaders who take us to the time when nobody ever has to say 'Me too' again."
It was a reference to the #metoo trend in which women have been sharing their experiences of sexual harassment by men, following the exposure of several powerful Hollywood figures, like producer Harvey Weinstein, over their behaviour.
The ideal post-Trump politician will, at the very least, be a deeply serious figure with a strong record of public service behind her. It would be a devastating, self-inflicted wound for the Democrats to settle for even benevolent mimicry of Mr Trump's hallucinatory circus act.
AUTHOR CHATTERTON WILLIAMS, who is working on a book on racial identity, wrote in the New York Times Magazine.
But it electrified a segment of America that, analysts say, was in need of inspiration, as each week serves up what they perceive as a new outrage from President Donald Trump.
That Ms Winfrey could take on Mr Trump is beyond doubt. In a survey of 1,000 likely voters after the awards night speech, the Republican-leaning Rasmussen Poll found 48 per cent would opt for Ms Winfrey if she ran for president, compared with 38 per cent who said they would vote for Mr Trump. A sizeable 14 per cent were undecided.
In another poll, 54 per cent of those surveyed did not want her to run for the 2020 presidency, although she would still beat Mr Trump if she did.
At 63, Ms Winfrey is a shade wealthier than the 71-year-old Mr Trump. She is also a lot of things that the President is not.
Ms Winfrey built her media reputation and empire from scratch, not off a hefty loan from her father. She made her name on empathy with her audiences across all social groups - not on a TV show that celebrated corporate ruthlessness.
Her messaging has always been inclusive and compassionate, not harsh and divisive.
Under the care of her father, she attended Nashville East High School and took to drama. She was elected school president and when rehearsing with her drama class was spotted by local radio station WVOL and offered a spot to read the news.
She later won a public-speaking contest and a scholarship to Tennessee State University, where she majored in speech communications and performing arts.
As her voice and empathy with audiences brought success, she was noticed by legendary musician and producer Quincy Jones and cast by him and Steven Spielberg in the acclaimed 1985 film The Color Purple.
At the Golden Globes, Ms Winfrey was presented with the Cecil B. DeMille Award for lifetime achievement - the first black female recipient. Her inspiring speech brought the audience to its feet.
"Don't underestimate the possibility of Oprah 2020," opinion writer Eugene Robinson wrote the next day in the Washington Post.
The idea of a bid for president has come up before, but Ms Winfrey has always said she was not inclined. Yet friends have said she may be.
Asked about it last week, Mr Trump said competing against Ms Winfrey in 2020 would be "a lot of fun" but he would win.
Many, however, have also cautioned against Oprah fever.
Author Chatterton Williams, who is working on a book on racial identity, wrote in the New York Times Magazine: "The ideal post-Trump politician will, at the very least, be a deeply serious figure with a strong record of public service behind her. It would be a devastating, self-inflicted wound for the Democrats to settle for even benevolent mimicry of Mr Trump's hallucinatory circus act."
A Democratic Party strategist told The Straits Times: "This Oprah movement says something about America that is disturbing.
"Why would they want another non-politician in the White House? Why are we looking at someone simply because they gave a great speech, and thinking we want them negotiating treaties? What cognitive disconnect makes us want this as a nation?"