Angie Smithson joined the trust almost three years ago and has since provided leadership throughout the pandemic.
She will retire in April after serving 36 years in healthcare.
Dr Hal Spencer, the trust’s current medical director, will take up the chief executive role in the interim before recruitment is expected to begin later in the year.
“We have a caring and successful organisation and continue to recruit and retain some of the very best colleagues in the country.
“It has been such a privilege to have worked in healthcare for the whole of my career and to have been the chief executive here at Chesterfield Royal Hospital.
“I have relished leading through these uncharted waters with a team that continue to go not only the extra mile but the extra marathon.
“You are a credit to the organisation, the NHS and the communities we care for.
She added: “My plan was to retire at this age – now feels like the right time to leave on a high.
“I will stay in position to provide a suitable handover and provide stability to the organisation that I am hugely proud of and I will be handing over to Dr Spencer as the interim chief executive from 1 April.
“I know Dr Spencer will offer clear and compassionate leadership during these challenging times.”
Angie’s career started in nursing in 1986.
She worked in nursing and midwifery while completing her degree.
She then moved into general management roles, completing an MBA, and has served in board director roles in foundation trusts for the last 14 years.
Dr Helen Phillips, chair of the trust, said: “We wish Angie all the very best for the future.
“Her leadership has been greatly appreciated during what has been an unprecedented period of challenge compounded by the effects of the pandemic.”