The vote on Isaacman, who Trump removed and then renamed as NASA administrator nominee this year, passed 67-30, two weeks after he told senators in his second hearing that NASA must pick up the pace in beating China back to the moon this decade.
Isaacman will lead an agency of 14,000 employees as it invests billions of dollars into its most ambitious space exploration endeavour yet: returning humans to the moon to seed a long-term presence on the surface before eventually sending astronauts to Mars.
The White House, in its government efficiency push led by Musk, slashed NASA's workforce by 20 per cent and has sought to cut the agency's 2026 budget by roughly 25 per cent from its usual $25 billion, imperilling dozens of space-science programs that scientists and some officials regard as priorities.
Isaacman envisions a revamped focus on sending missions to Mars on top of the Artemis moon effort, as well as a greater dependence on private companies such as SpaceX to save taxpayer money and stimulate private-sector competition.
Of the 67 votes in Isaacman's favour, 16 were from Democrats, joining 51 from Republicans. All 30 votes against his confirmation were from Democrats.
Maria Cantwell, the ranking member of the Senate Commerce Committee that oversees NASA, has criticised the Trump administration's efforts to cut NASA's science unit. She supported Isaacman's confirmation on Wednesday.
"During his nomination process, Mr Isaacman emphasised the importance of developing a pipeline of future scientists, engineers, researchers, (and) astronauts to support the science and technology development and align with NASA's objectives. I strongly agree," Cantwell said.
Some Democratic senators said during Isaacman's hearing on December 3 they are concerned about Isaacman's closeness to Musk, whose company holds about $US15 billion in NASA contracts and could benefit from certain policies Isaacman has advocated.
Musk advocated for Isaacman's nomination when Trump was elected in 2024. Musk had sought to realign the US space program with a greater focus on Mars during his stint as a close adviser to Trump.
Senate Republicans and some Democrats, including Cantwell, have also stressed urgency in NASA's moon race with China, which is aiming to send its astronauts to the lunar surface by 2030. NASA faces a shaky target of 2028 using its Space Launch System rocket and SpaceX's giant Starship rocket, under development, as the lander.
