The charity is responsible for the management of six historic sites including Hampton Court Palace and Tower of London.
Ms Worsley, who is well known for historical TV documentaries and as an author, has held the role for 21 years.
She specialises in the Tudor period to the present day.
In statement on X, she says she wants to spend more time growing her Lady Killers community.
The podcast which Ms Worsley hosts, investigates the crimes of women in the past from a contemporary, feminist perspective.
Historic Royal Palaces has released a statement on X, it reads:
“Thank you, Lucy, for being a wonderful colleague to us all and for the extraordinary contribution you’ve made to our charity.”