Mike Davies is to leave Telegraph Hill secondary, Lewisham, south-east London, after learning that it was to be placed in special measures.
The announcement came less than a year after the school was relaunched under the beleaguered Fresh Start policy.
In a letter to parents, the school's chair of governors, Madeliene Long, said Mr Davies had shown "real commitment" since assuming the new position last year.
"He has made his contribution with his particular set of skills. However, he and I agree that a different approach is needed now as the school moves into a new phase," she wrote.
The governing body and Lewisham council are now looking for a new headteacher to tackle Telegraph Hill's problems.
The school is to close for six days at the end of this term and the start of next to allow for extra staff training.
Last week, Richard Ewen, who had been assisting Mr Davies as a "consultant head" at Telegraph Hill, was announced as the new principal of Islington Arts and Media School, the failing Fresh Start comprehensive in north London.
O the first nine secondaries to be picked up by the Fresh Start programme - a process which sees a struggling school close and re-open with a new name, new management and new teachers - three of them have since been put in special measures.
And one of the other schools, Firfield community college, in Newcastle, has been earmarked for closure after repeatedly failing to arrest a downward slide in its pupil numbers.
John Bangs, assistant secretary of the National Union of Teachers, said: "I have sympathy with the head, and sympathy with the staff at Telegraph Hill, because Fresh Start is a failed policy.
"It's been a disaster. It's totally unfair on heads and staff to expect turnarounds within a few months when many of the pupils they educate come from very deprived backgrounds.
"Schools need five or six years to be turned around, and they are not being given that time."
Meanwhile, the Department for Education and Employment last week held a meeting for heads of all the Fresh Start schools.
Among the issues covered were strategies for recruiting teachers, sharing ideas and advice, and the monitoring work carried out by the Office for Standards in Education.