Stephen Porter will retire in April 2013 after 21 years at the helm. Porter took over as chief executive of what was then Manchester Methodist Housing Association in 1991.
He steered the organisation through several mergers and name changes before it became Great Places Housing Group in 2006.
No successor has been named yet. The position will be advertised externally in the coming month.
Porter said: "I've had the amazing privilege and pleasure to have been chief executive of Great Places for so many years. For me, what makes us so special is the people who work here and I am immensely proud of all that we have achieved.
"I am sad to be going and will miss working with so many talented and enthusiastic people, but now is the right time to move on.
"We have grown over the years but our can-do culture, and focus on providing excellent services for our customers, has remained the same and I know that will continue to be the case."
Great Places now manages more than 16,000 homes across the North West and South Yorkshire. It also provides 1,500 supported housing units for people with drug or alcohol problems, or mental health issues.
The organisation recently became the first exclusively Northern-based housing association to issue a bond, raising £200m to fund its development programme.
Great Places also has the largest development programme of any housing association outside the South East, and every year rehouses over 3,000 households.