Pauline Montalto, head of school at Thomas Bennett Community College, has resigned.
Ms Montalto, who has been part of the school team for 30 years, will leave in the summer.
She will be replaced, on an interim basis, by Gianni Bianchi, executive head at the Bewbush Academy, which is also part of the TKAT (The Kemnal Academies Trust) family.
In a letter to parents, chairman of governors Dick Brown said Ms Montalto's resignation had been accepted "with reluctance".
He added: "Mr Bianchi is a highly experienced headteacher with a strong track record of uniting staff, raising standards and bringing about rapid improvement."
The news followed last week's announcement that 12 of the school's teachers and a number of support staff had resigned since Easter.
In addition, the National Education Union (NEU) announced four days of strike action.
The concerns of staff and parents centre around plans by TKAT to cut £987k from the school’s budget. While the Trust said it was undertaking a "restructure", the union said at least 22 teachers and support staff would lose their jobs.
Teachers and support staff from the school, in Tilgate, will strike on Thursday June 21, Tuesday June 26, Wednesday June 27 and Thursday June 28.
On Saturday, parents, staff and children held a march and rally in Crawley town centre to show their support for the school and its teachers.
Whistles blowing and banners flying, they marched from the town hall to Queens Square, where a number of speakers shared their stories and concerns and appealed to people not to be silent over the issue.
Speaking in Queens Square, organiser Kerry Flynn said: "It is imperative that we take the fight to the Regional Schools Commissioner and make sure our children receive the education they deserve.
"The cuts at Thomas Bennett will not be the first cuts. We need to take a stand now."
Parent Emma Ford, added: "Thomas Bennett, as a school, I have always found to be an holistic, student-focused school. The dedication from the staff and the caring from the staff has been absolutely amazing.
"By reducing the number of teachers at this school, how is that going to continue? How are staff going to have the time and the resources to be able to continue to treat each child as an individual and get the best out of each child?"
Video footage by Carol Vincent.