In a statement, Chief Executive Carrie Lam said she had submitted Lee’s resignation letter to the central government in accordance with the Basic Law.
Lee will go on leave with immediate effect.
He is expected to hold a press conference at 5.30pm on Wednesday.
Lee was the first number two official in Hong Kong with a police background, taking on the position after a stint under the Lam administration as security secretary.
During his time in the two roles, he has handled a number of hot-button issues, from introducing a joint-immigration checkpoint with the mainland at the West Kowloon high-speed rail terminus, to banning the pro-independence Hong Kong National Party in 2018.
In 2019, he apologised after the administration’s ill-fated extradition bill sparked months of social unrest.
“I have expressed my apology. And I expressed my apology because as the chief executive said, it is because of the inadequacy of our work,” he said.
After succeeding Matthew Cheung as chief secretary in 2021, Lee brushed aside concerns about what some saw as his lack of policymaking experience.
“There is no know-all, I think, in this world. I have strengths,” he said.
Lee, who’s 64, joined the police force in 1977 as an inspector. He rose through the ranks and became the deputy police commissioner in 2010.
In 2012, he joined the CY Leung administration as the under secretary for security.