Chris Butler will step down as chief executive of Leeds and York Partnership Foundation Trust at the end of December, after 10 years in the post.
The trust said he wants to explore other career opportunities.
Mr Butler, who was previously in charge of Kingston Primary Care Trust, was named in the top 50 chief executives by the HSJ in March.
The FT has had a difficult year, being rated as “requires improvement” by the Care Quality Commission in January, before losing a major community mental health contract in York.
Mr Butler said: “I have enjoyed 10 years here at the trust and I have had the privilege of working with fantastic people who are dedicated to improving the health and lives of people who use our services.
“The NHS and social care is facing unprecedented changes if it is to survive and my view is that the trust needs a person at the helm who is in it for the medium term.
“At such a late stage in my career I have come to the conclusion that the time is right for me to hand over the reins to someone who can do just that.”
Trust chair Frank Griffiths said: “During his time with the trust he has taken the time to get to know hundreds of people, including many service users and carers, and he will be greatly missed by many people.”
Information provided to HSJ