England and Wales Cricket Board chief executive Tom Harrison will step down from the role in June.
Harrison was appointed in 2014 and oversaw the introduction of The Hundred, which started last year.
Former England captain and women's cricket managing director Clare Connor will take over on an interim basis amid a turbulent period for English cricket.
Harrison said he had "put everything into this role" but "now is the right time to bring in fresh energy".
England men's cricket has already undergone an extensive overhaul in the past three months after the heavy Ashes defeat in Australia over the winter.
Brendon McCullum has taken over as men's Test coach, with Ben Stokes replacing Joe Root as Test captain and Rob Key appointed managing director.
The England and Wales Cricket Board (ECB) is still searching for a new chairman following the departure of Ian Watmore in October.
Harrison's tenure since replacing former chief executive David Collier has been controversial.
In 2017 he oversaw the signing of a £1.1bn TV rights deal with Sky Sports and the BBC that runs until 2024, and England also won the men's and women's 50-over World Cups during his term, in 2019 and 2017 respectively.
But the introduction of The Hundred has been contentious, some questioning its impact on the wider game and domestic schedule, and in recent years there has been a decline in the fortunes of the men's Test side. They have only won one of their past 17 Tests and and none of the past nine.
Harrison also spoke in front of MPs at the Digital, Culture, Media and Sport select committee amid the Azeem Rafiq racism scandal which engulfed English cricket in November.
During his testimony Harrison said the ECB was "fit for purpose" but apologised to those who had suffered abuse and said "we know we may have let you down".
In 2020 the ECB cut 62 jobs as a result of the impact of the coronavirus pandemic, despite managing to fulfil England's fixture list after Covid-19 halted sport across the world.
Harrison was heavily criticised the following year when it was reported he and a group of senior executives were to share £2.1m in bonuses.
"The past two years have been incredibly challenging, but we have pulled together to get through the pandemic, overcome cricket's biggest financial crisis, and committed to tackling discrimination and continuing the journey towards becoming the inclusive, welcoming sport we strive to be," Harrison said.
Interim chair Martin Darlow said: "When the pandemic struck, it was Tom's leadership that brought the game together and saved us from the worst financial crisis the sport has ever faced.
"He has always put the interests of the game first and worked to lead important change to make our game more accessible and inclusive."
The job vacancy to replace Harrison will be advertised by the ECB shortly.
Connor will continue as managing director of women's cricket, though the ECB will look at bringing in support for the role when she takes up the chief executive interim post, while she will also continue to chair the ICC Women's Cricket Committee.
Actor and writer Stephen Fry will take over from Connor as the next president of the Marylebone Cricket Club in October.
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