The TV personality would have a 10-point lead over the Republican if a vote were held today, a Rasmussen Reports survey found.
Speculation that Ms Winfrey could run for the White House in 2020 has swirled since she gave a rousing speech at the Golden Globe Awards, praising women who have spoken up against sexual violence and promising “a new day”.
Friends of the celebrity have said she is ”actively considering” running against Mr Trump, although she has denied any presidential ambitions. The President himself, meanwhile, said “I don’t think she’s going to run” and boasted he would beat her if she did.
However, the new poll suggests 48 per cent of likely US voters would opt for Ms Winfrey if she did enter the fray, compared to 38 per cent who said they would vote for Mr Trump. A sizeable 14 per cent were undecided.
More than a fifth of Republicans would back Oprah, found the poll, thought to be the first to test Ms Winfrey’s popularity against that of Mr Trump.
Seventy-six per cent of Democrats, 22 per cent of Republicans, and 44 per cent of unaffiliated voters surveyed said they would vote for the former talk show host and entrepreneur.
The President would earn 66 per cent of the Republican vote, as well as 12 per cent of Democrats and 38 per cent of those with no affiliation, according to the survey.
Mr Trump said this week he did not think Ms Winfrey would run for the White House, noting that he knew her “very well” and had appeared on one of the final episodes of The Oprah Winfrey Show.
The President will have surprised few observers with his predicted outcome of any future White House race against Ms Winfrey.
Yeah, I’d beat Oprah,” he said. ”Oprah would be a lot of fun. I know her very well. I did one of her last shows. She had Donald Trump - this is before politics - her last week, and she had Donald Trump and my family, it was very nice.”
But he added: “I don’t think she’s going to run.”
The President has spoken warmly of Ms Winfrey in the past, tweeting in 2012: “I adore Oprah.”
The majority of Americans share his affection, according to the Rasmussen Reports research, which found 55 per cent of voters view her favourably. The poll surveyed 1,000 likely voters by phone and online.
Some pundits have warned running for the White House could damage Ms Winfrey, noting approval ratings tend to crash immediately once an individual announces their intent to run for office, and pointing to her lack of political experience as a potential obstacle.
After four years of Mr Trump, some suggest, the US public may want to elect a leader with legislative experience.
However, celebrities and pundits alike have expressed interest in an Oprah 2020 campaign, noting that - unlike Mr Trump - she is a self-made billionaire, and that she already has near-ubiquitous name recognition in the country.
Candidates for the 2020 election are not likely to officially announce runs until after the mid-term elections later this year.