Zacharia was "let go" and is "transitioning out" of the press secretary position, according to two separate White House officials.
She faced days of questions about her legal credentials and criticism of her performance in a news briefing and interviews.
The departure leaves Trump without a key public messenger just over two weeks before November's midterm elections, a critical period when the president is seeking to tout his administration's accomplishments and help his fellow Republicans retain control of Congress.
Trump told reporters earlier on Friday that he had asked Zacharia to reconsider whether to continue in her role after facing tough press coverage during her first days on the job.
"I told her: 'I think you're better off being happy, and I'm not sure you can ever be happy in this stuff.' There's nothing easy about this stuff," he told reporters as he departed the White House for a weekend trip.
He added: "I said to her honestly, 'If I were you, I'd reconsider... think about it. But I would reconsider.'"
Zacharia started on Monday and held her debut White House briefing on Tuesday. She said she received a call about the press secretary role on October 7 and was offered the job to succeed Karoline Leavitt a week ago.
She soon faced questions about her career, which she said included a tenure practicing law. Trump had also described her as a lawyer.
"I practiced international transaction law, with all the appropriate credentials," Zacharia said in an emailed statement on Wednesday.
Reuters could not find records showing the Pepperdine University law school graduate was registered as an attorney or member of the bar in any US state or the District of Columbia.
During a Fox News interview on Thursday, Zacharia said she did not pass the bar exam. Law school graduates cannot legally practice law in the US without first being admitted to a state bar.
Zacharia and the White House did not immediately respond to an email seeking comment about her firing.
Trump hired Zacharia after expressing concerns about the media coverage of his administration, feeling he needed a new spokesperson who could amplify his achievements, according to two people familiar with the conversations.
In a phone interview with Fox on Friday, Trump said he was in no rush to name a new press secretary.
Zacharia's quick exit meant she had what is believed to be the shortest tenure of any press secretary in the role's history.
"Records are made to be broken," Anthony Scaramucci, who served as director of communications for 10 days during Trump's first administration, said on X. "But I take no pleasure in other people's pain."