Clare Connor, the former England captain who already holds a number of roles with the ECB, MCC and ICC, takes over on an interim basis while a new CEO is located.
Harrison’s departure had been expected for some time, and he becomes the latest senior figure to leave the governing body this year.
After the Ashes, managing director of men’s cricket Ashley Giles and head coach Chris Silverwood were fired, before Joe Root resigned as Test captain.
The ECB have also been conducting an increasingly farcical search to locate a new chairperson, after Ian Watmore resigned in October.
Harrison said: “It has been a huge honour to be CEO of the ECB for the past seven years. Cricket is an extraordinary force for good in the world and my goal has been to make the game bigger and ensure more people and more communities in England and Wales feel they have a place in this sport.
“The long-term health of cricket depends on its ability to grow and remain relevant and be more inclusive in an ever-changing world.
“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. I have put everything into this role, but I believe now is the right time to bring in fresh energy to continue this work.”