Trump said last December, before returning to office, that he wanted the online payments entrepreneur and the first private astronaut to conduct a spacewalk to serve as the next head of NASA.
But on Saturday, he said on his Truth Social platform that "after a thorough review of prior associations, I am hereby withdrawing the nomination of Jared Isaacman to head NASA."
"I will soon announce a new Nominee who will be Mission aligned, and put America First in Space."
Earlier Saturday, the New York Times had reported the move was coming, quoting unnamed sources as saying the decision had come after the president learned Isaacman had donated money to prominent Democrats.
Asked about that report, the White House had told AFP in an email that it was "essential that the next leader of NASA is in complete alignment with President Trump's America First agenda."
"The Administrator of NASA will help lead humanity into space and execute President Trump's bold mission of planting the American flag on the planet Mars," it said.
The nomination shakeup appears to be a snub of billionaire Musk, who on Friday stepped back from his role leading Trump's so-called Department of Government Efficiency (DOGE).
Musk reportedly lobbied directly with the president for Isaacman, who has had significant business dealings with Musk's SpaceX, to get the top NASA job, raising questions of possible conflicts of interest.
As the news surfaced, Musk stressed on X that "it is rare to find someone so competent and good-arted".
The 42-year-old founder and CEO of Shift4 Payments has emerged as a leading figure in commercial spaceflight through his high-profile collaborations with SpaceX.
He made history last September by stepping out of a Crew Dragon to gaze at Earth from the void of space while gripping the spacecraft's exterior, during the first-ever spacewalk carried out by non-professional astronauts.
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