McDonald will leave the entertainment specialist at the end of the year to take time out with her family. She plans to take on general consultancy work for Outside next year.
The news comes a week after it emerged the agency's international director Celena Aponte was returning to the US.
CEO Alan Edwards said: ‘I understand why Penny has decided to leave, but am sure we will be hooking up on projects in the near future.'
McDonald was hired as the entertainment specialist's first MD in February 2007.