Mr Zinke was among Mr 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.
His departure makes him the ninth Cabinet-level official to leave a post since Trump took office two years ago.
Zinke's resignation letter, obtained from a Zinke aide on Saturday, cites what he calls "meritless and false claims" and says that "to some, truth no longer matters".
"On his first day in office, Mr. Zinke rode a horse to work, in plain imitation of Teddy Roosevelt".
Mr Zinke played a leading part in President Trump's efforts to roll back environmental regulations and promote domestic energy development. "A well-managed Interior Department - one that puts the public good ahead of fossil fuel and mining industry demands - can be a boon to the entire country".
Meanwhile, conservation groups slammed Zinke, calling him a danger to the environment.
U.S. President Donald Trump walks past Interior Secretary Ryan Zinke as he stands to address the 17th annual September 11 observance at the Flight 93 National Memorial near Shanksville, Pennsylvania, U.S., September 11, 2018. But a series of crises, including wildfires in the West and uncertainty over whether John Kelly would stay on as White House chief of staff, had afforded Zinke a temporary reprieve.
The secretary's final public appearance was Thursday night at his Christmas party, which he told White House staffers he wanted to have before his dismissal.
Zinke has also come under fire for weakening conservational protections of wildlife and American lands.
The most serious of the allegations, according to US media reports, focuses on whether Zinke used his power as interior secretary to gain personal profit in a land deal in his hometown of Whitefish, Montana.
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An investigation was reportedly launched, among others, into the real estate deal struck between a foundation established by Zinke and a group supported by the chairman of the Halliburton oil service company, which could have constituted a conflict of interest. Zinke has denied wrongdoing.
Zinke's tenure was also marred by mounting ethics inquiries into his travel and personal financial dealings, among others.
The Interior Department inspector general referred the land deal scandal to the Justice Department. Then there was the department spending more than $25,000 on security for Zinke and his wife when they traveled to Turkey and Greece.
It's the latest high-profile departure from his administration.
"I think I'm probably going to be the commander of space command", Zinke said. Grijalva, who in the past had acknowledged having a problem with alcohol but said it had been addressed, said the committee would not be distracted from examining Zinke's actions. Pruitt resigned in July.
Senate Minority Leader Chuck Schumer was scathing in response to the news that Zinke was leaving.
"The swamp Cabinet will be a little less foul without him", Schumer said. "However, after 30 years of public service, I can not justify spending thousands of dollars defending myself and my family against false allegations", Zinke wrote on Twitter following news of his resignation.
Grijalva spokesman Adam Sarvana said Saturday that committee leaders still meant to ask for Zinke's testimony.
Sullivan and fellow Republican Sen.
Under Zinke's watch, the Interior Department moved to auction off more oil leases, ended a moratorium on new sales of federally owned coal, and repealed mandates governing drilling.