The college, which has bases in Corby, Kettering and Wellingborough, was branded ‘inadequate’ by regulators Ofsted just last month.
Leadership and management were highly criticised after the inspection of the college, which provides education for more than 4,000 students in the north of the county.
It was also announced earlier this year that the college would controversially stop providing A-level courses.
Simon Evans, chair of governors at Tresham College, thanked Mr Wesselby for the work he has done.
He said: “It is with regret that I must confirm that Stuart Wesselby has decided to step down as principal of Tresham College of Further and Higher Education with effect from September 30, 2016.
“I would like to thank Stuart on behalf of the college for the contribution he has made to the development of the college and its students during his time as principal, most recently by securing the funding for the Wellingborough campus development.
“Stuart has always been a passionate advocate of Tresham, its students and staff and I wish him well in all his future plans.”
For the immediate future, Corrie Harris (vice principal for curriculum and quality) will take the role of interim principal pending the recruitment of a longer term appointment.