The mayor's office says Amir Remtulla, who has served Ford for 18 months, will leave his post on July 20 to become vice president of external partnerships for the 2015 Pam Am Games.
Remtulla says serving Ford has been "an honour and a privilege."
The mayor's office says Remtulla has been credited with helping steer a number of key items through city council, including the budget, the outsourcing of garbage collection and successful labour negotiations with a number of Toronto workers.
Remtulla took over as Ford's chief of staff in February 2011, after helping the mayor transition into office.
Ford says Remtulla brought "tremendous leadership" to his team.
"His experience, advice and dedication to his work will be missed. I would like to thank him for his service," the mayor said in a release.
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