"Yeah, I'll beat Oprah," he told reporters in the the Cabinet Room during a meeting on immigration with members of Congress.
Winfrey is "intrigued by the idea" of a presidential bid, best friend and CBS "This Morning" co-anchor Gayle King said Tuesday, and is taking the idea seriously, per friends of the former talk show host. Her speech on the #MeToo movement at Sunday's Golden Globes propelled Winfrey to the forefront of political conversation on Monday, with the potential to disrupt the Democratic primary process and pose a strong challenge to Trump in 2020.
"Oprah will be a lot of fun," Trump said Tuesday, noting that he knows Winfrey "very well" and appeared with his family on one of the final episodes of "The Oprah Winfrey Show."
"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," the President said.
Trump has tweeted warm words for Winfrey many times before taking office, even saying, "I adore Oprah" in a 2012 tweet
And in a 1999 interview with Larry King, he said she would be "always be my first choice" for a running mate.
"She's popular, she's brilliant, she's a wonderful woman," he said at the time. "It would be a pretty good ticket."
But Trump said Tuesday he doesn't think she will ultimately put her name in the ring.
"I like Oprah, I don't think she's going to run," he said, repeating, "I don't think she's going to run."
The White House continued to field questions about a potential Winfrey candidacy Tuesday afternoon.
Asked what advice she would give a political outsider looking to run for president, press secretary Sarah Sanders declined to engage.
"I'm not going to focus on anyone's campaign other than President Trump's re-election," she said at the daily briefing.
Asked whether Winfrey was qualified, Sanders said, "Look, I disagree very much on her policies," although Winfrey has no voting record.
"Is she a successful individual? Absolutely. But in terms of where she stands on a number of positions, I would find a number of problems with that," Sanders said.
CNN's Brian Stelter and Elizabeth Landers contributed to this report.