President Trump tweeted about Zinke's departure Saturday morning.
Zinke was among Trump's most active Cabinet members, cutting huge wilderness national monuments in Utah to a fraction of their size and proposing offshore oil drilling in the Arctic, Pacific and Atlantic.
He also faced the prospect of congressional probes after newly elected Democrats take majority control of the House.
Senate Democratic leader Chuck Schumer applauded Zinke's departure in a tweet. "The Trump Administration will be announcing the new Secretary of the Interior next week".
"The swamp Cabinet will be a little less foul without him", Schumer said.
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But Labour leader Jeremy Corbyn said: "The last 24 hours have confirmed that Theresa May's Brexit deal is dead in the water". The pair has a public bust-up after reports that the European Commission president had called May "nebulous".
On Saturday, Trump announced that Zinke would step down at the end of this year after two years in office.
Zinke tied his departure to the burden of "false allegations" against him.
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Arizona Rep. Raul Grijalva, the top Democrat on the House Natural Resources Committee, had warned that after Democrats took control of the House they meant to call Zinke to testify on his ethics issues.
The Justice Department is investigating Zinke for allegedly using his office for personal gain, following a referral from the Interior Department's inspector general.
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Mr Corbyn labelled Theresa May's government as the "most shambolic and chaotic" in British history. She said the vote would be held the following week.
Like Treasury Secretary Steven Mnuchin, Energy Secretary Rick Perry, former Veterans Affairs Secretary David Shulkin and former EPA head Scott Pruitt, Zinke has also been accused of abusing taxpayer funds for flights.
Neither the White House nor the Interior Department responded to TheDCNF's requests for comment.
"It's hard for him to think straight from the bottom of the bottle", Zinke wrote from his official Twitter account on November 30.
Zinke says the allegations are a farce, and pointed out on Twitter Saturday that he's been subject to a constant stream of Freedom of Information Act requests and politically motivated attacks since taking office, largely, he seems to feel, because he's been instrumental in rolling back restrictive Obama-era environmental policies that choked off industry and failed to move the cause of conservation forward.
Murkowski remains chairman of the Senate Committee on Energy and Natural Resources as well as the Interior-Environment Appropriations Subcommittee.
Previously, the president had repeatedly praised Zinke's performance at Interior.
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It will hope that fear of the chaos that a no-deal exit might bring will force lawmakers to put aside their reservations. Last night, the Conservative party declared that she had survived by 200 votes to 117.
Two outgoing Republican congressmen are said to be interested in the job.