President Volodymyr Zelensky’s powerful chief of staff, Andriy Yermak, resigned on Friday in the highest-level political realignment in Ukraine since Russia’s all-out invasion nearly four years ago.

The departure of Mr. Yermak, who had headed Ukraine’s negotiating team in peace talks with the Trump administration, put in doubt the future of the latest round of diplomatic efforts by the United States, Ukraine and European nations to end the war.

It also cost Mr. Zelensky a longtime close ally who had been a behind-the-scenes operator, a political enforcer and, as Ukraine’s fortunes in the war slumped, a lightning rod for criticism over much of what had gone wrong, including allegations of theft from state companies.

Mr. Yermak stepped down amid a spiraling, $100 million embezzlement scandal that has already led to the dismissal of two cabinet ministers and even threatened to topple Mr. Zelensky’s entire cabinet.

“I am grateful to Andriy for always representing Ukraine’s position in the negotiation track exactly as it should be represented,” Mr. Zelensky said in a video address announcing the resignation. He said he had accepted the resignation to “avoid rumors and speculation” about his chief of staff.

Mr. Yermak, 54, is the highest-level official to lose his job in the fallout from the 15-month investigation called Operation Midas, revealed by Ukraine’s top anti-corruption agencies, which said the effort had produced 1,000 hours of wiretaps.