"This week will always have a little bit of bittersweet to it," Nutter said. "He is out front when he needs to be, but I have never met a more selfless person."
Director of policy Suzanne Biemiller will serve as interim chief of staff.
Armbrister, who previously served as Chief Operating Officer of Temple University, has been with Nutter since he took office, steering the city through years of financial hardship and tough budget battles. He has also served as managing director of the school district and city treasurer.
A spokesman for the mayor declined to comment.