As with most announcements from the current administration, the US president announced he had accepted Pruitt’s resignation in a tweet.
Pruitt is the subject of 14 federal investigations into his conduct as EPA chief, including mismanagement of funding.
The New York Times newspaper reported new questions about whether Pruitt’s aides had "deleted sensitive information about his meetings from his public schedule, potentially in violation of the law".
Pruitt was also found to have broken the law when he spent $43,000 on a secure telephone booth for his EPA office.
He is under investigation for leasing a bedroom in a condominium connected to a lobbying firm, which had worked on behalf of a Canadian energy company, The New York Times said.
Other reported scandals included asking an aided to source a used mattress from a Trump Hotel, using his position to reach out to the chief executive of a fast food chain in a bid to help his wife open a franchise of the restaurant, and his use of first-class travel, ostensibly to avoid harassment by members of the public.
Pruitt was instrumental in convincing the president to withdraw from the Paris Climate Agreement on 1 June 2017.
Pruitt had been criticised by members of both main political parties in the US in recent weeks over his actions, including from within the administration, according to reports.
In his resignation letter, obtained by the New York Times, Pruitt cited "unrelenting attacks" on him and his family, which he claimed were "unprecedented" and had "taken a sizable toll".
Trump praised Pruitt for the work he did, mostly rolling back environmental protections, and named EPA deputy Andrew Wheeler as the acting administrator until the US congress can confirm Pruitt’s successor.
Wheeler is a former coal industry lobbyist and previously an aide to Oklahoma senator Jim Inhofe, who famously took a snowball on the floor of the US senate to serve as evidence against climate change.
Even Pruitt’s appointment in February 2017 to lead the agency tasked with enforcing US environmental legislation was heavily criticised.
The climate-change sceptic had made a career out of suing the agency while Attorney General for his home state of Oklahoma.
Pruitt becomes the 38th high profile member of the Trump administration to resign, be forced to resign, or be fired in just over 500 days of the presidency.