No reason was given for the departure of Driscoll, who is a friend of Vice President JD Vance, but tensions with Defense Secretary Pete Hegseth have been widely reported.
It marks the latest in a series of shakeups of the military leadership, with the Army especially seeing major upheaval.
"Secretary Driscoll has been highly effective in advancing President Trump's agenda to Make America Strong Again at the Department of the Army by providing outstanding leadership during historic military operations, restoring an emphasis on readiness and lethality, assisting with negotiations between Russia and Ukraine, and more," White House spokeswoman Anna Kelly said in a statement.
"The United States Army is more powerful than ever thanks to his work alongside the Commander-in-Chief and Secretary of War," she added.
A US Army official, who was not authorised to comment publicly confirmed that Driscoll had submitted his resignation.
The Pentagon referred questions to the Army.
Hegseth suddenly ousted the service's top uniformed leader, General Randy George, in April, while the Army's commander in Europe and Africa, General Christopher Donahue, unexpectedly stepped down in June.
General Christopher LaNeve, who has made a meteoric rise under Hegseth, took George's place as the Army's acting chief of staff.
Under LaNeve, the service is pulling the plug on a drone modernisation program that Driscoll had heralded.
An Army unit based in Europe was building its own drones before LaNeve directed it to end its efforts and return to being a traditional infantry battalion, officials said in August.
Driscoll was a George ally and lamented his departure, along with both Republican and Democratic lawmakers. He told Congress in April that he and his family drove to George's house following his resignation "and we all gave him a hug".
Driscoll is an Iraq war veteran, tech investor and former adviser to Vance, whom Driscoll met at Yale Law School.
As Army secretary, Driscoll was tapped for the unusual role of key negotiator to try to end the war between Russia and Ukraine.
He was also a major force behind trying to cut the red tape for military contractors to quickly develop more drones and counter-drone capabilities as warfare rapidly changes around the world.
Driscoll noted that his father and grandfather served in the Army and he vowed to be a secretary focused on the needs of soldiers. According to the Army, Driscoll served as an armour officer from August 2007 to March 2011, deploying to Iraq from October 2009 to July 2010.
with Reuters
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