Teesside MP Simon Clarke has resigned from the government for personal reasons.
In his letter to Boris Johnson, the Middlesbrough South and East Cleveland MP talked about "balancing my own life against the demands of office".
He was appointed to the Ministry of Housing, Communities and Local Government in February after moving from the Treasury.
Mr Clarke will continue as an MP and says he hopes to return in the future.
Writing to the Prime Minister, he said: "I would not have made this decision unless I believed it was of the utmost importance."
He added: "It has been a privilege to serve as a minister in your administration."
As minister for regional growth and local government, his responsibilities included the local authority resilience forum's Covid-19 response and devolution.
BBC Look North political correspondent Luke Walton said: "This is a significant announcement and will come as a surprise to supporters and opponents alike.
"Simon Clarke was widely seen as a Government high flyer, in a key job."