She is the third head to quit the fresh start school, now called East Brighton College of Media Arts (Comart), in five years. The advertisement for her successor appears in The TES today.
Dr Clough, said when she arrived in January 2001 from fee-paying Wimbledon high that she would stay for at least five years. But, despite securing the school's removal from special measures a year ago and winning praise from inspectors for her "tenacity and imagination", she felt frustrated in her efforts to make real headway.
Last term, with the school running only half full, results still at the bottom of the local GCSE table, a public finance initiative building scheme causing daily crises and three senior managers about to depart, Comart faced fresh uncertainty.
Options considered by Brighton and Hove council included federation with nearby schools. Dr Clough, meanwhile, investigated turning the school into a city academy - a privately-sponsored independent state school.
The council supported the move but released news of it before it had been discussed with staff and governors. The plan fell through because of concerns about the PFI scheme.
Now the council's plan is for Comart to form part of an "excellence cluster" based on Varndean, a beacon school.
Dr Clough, 58, left the school at the end of last term. Her doctor advised her to take early retirement. Jenny Pick, the acting principal who was brought in by the council at Christmas on the recommendation of the Department for Education and Skills, will continue in her role until the end of the current academic year.
Dr Clough, who is understood to be living in the Lake District, said this week that she was "extremely proud" to have been involved in taking the school out of special measures.
"I am convinced the staff and pupils of Comart have a very bright future ahead of them," she said.
Pat Hawkes, who chairs the council's schools committee, said Dr Clough had done an "outstanding job".
"We want someone who will carry on her work," she said. "It'll be interesting to see if there are people with the verve and determination to take it on."