Even as Hegseth, a former Fox News host, moves quickly to reshape the department, firing a general during wartime is almost without precedent.
The Pentagon confirmed that George, who had more than a year left in his term, "will be retiring from his position as the 41st Chief of Staff of the Army effective immediately".
The Pentagon said it was grateful for George's decades of service.
"We wish him well in his retirement," it said on Thursday.
Two defence officials, speaking on the condition of anonymity, said Hegseth has also fired General David Hodne, who leads the army's Transformation and Training Command, and Major General William Green, head of the army's Chaplain Corps.
The department did not give a reason for George's departure, which comes as the US military builds up its forces in the Middle East while carrying out operations against Iran.
The US strikes in the region are largely being carried out by the navy and air force, although army soldiers have been dispatched to the Middle East for air defence systems.
The army is the largest branch of the US military, with about 450,000 active-duty soldiers.
Thousands of soldiers from the US Army's elite 82nd Airborne Division have also started arriving in the Middle East, potentially for ground operations in Iran.
There had been no public signs of friction between Hegseth and George, even as Hegseth pursued controversial moves such as firing the army's top lawyer and arranging a massive military parade to celebrate the army's 250th birthday, which coincided with Trump's birthday.
Hegseth this week also reversed an army decision to investigate army pilots who were flying attack helicopters near singer Kid Rock's house, in an apparent show of support for the vocal Trump backer.
CBS News said it was not related to the Kid Rock incident.
One of the officials said Hegseth's former military aide and army vice-chief of staff, General Christopher LaNeve, will take over George's role in an acting capacity.
George, who served in Iraq and Afghanistan, was confirmed to the top army post in 2023.
He was considered close to Army Secretary Dan Driscoll.
The two worked together to take on large defence companies, in the army's drive to speed up weapons development and drive down costs.
George's removal adds to recent upheaval at the Pentagon, including the firing in 2025 of the previous chairman of the Joint Chiefs of Staff, Air Force General CQ Brown, as well as the chief of naval operations and air force vice-chief of staff.
with AP
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