Mel Higgins was appointed 18 months ago and was the fifth chief executive in the 12-year history of the company.
Ilex has faced criticism in the past for failing to fill its top job.
Its first chief executive, Rick Reinhard, lasted 11 months, while the longest serving chief executive, Aideen McGinley, was in post for just over three years, between 2009 and 2012.
Ilex had difficulties filling the vacancy, and by 2013 the issue was being raised in Stormont, and the Office of First and Deputy First Minister admitted a public recruitment competition had not found any suitable candidates.
In the end Mr Higgins filled the position, first on an interim basis, before being appointed chief executive 18 months ago.
He is now leaving to take up a position at the Northern Regional College.
Ilex lists among its successes the Peace Bridge, the City of Culture year and the Science Park at Fort George.
Its ongoing projects include the One Plan and the redevelopment of the Ebrington Army barracks site.
In a statement, Ilex chairman Philip Flynn paid tribute to Mr Higgins, saying he very much regretted his departure.
Mr Flynn said he  is already engaging with OFMDFM to ensure a suitable successor is in place by the time of Mr Higgins' departure on 30 November.
The chief executive of Londonderry's urban regeneration company, Ilex, has resigned.