The fast food giant said Easterbrook "demonstrated poor judgment involving a recent consensual relationship with an employee".
McDonald's forbids managers from having romantic relationships with direct or indirect reports.
In an email to employees, Easterbrook acknowledged he had a relationship with an employee and said it was a mistake.
"Given the values of the company, I agree with the board that it is time for me to move on," Easterbrook said in the email.
McDonald's board of directors voted on Easterbrook's departure Friday after conducting a thorough review.
The board of directors named Chris Kempczinski, who recently served as president of McDonald's USA, as its new president and CEO.
Kempczinski was instrumental in the development of McDonald's strategic plan and oversaw the most comprehensive transformation of the US business in McDonald's history, said Enrique Hernandez, chairman of McDonald's board, in a statement.
"Steve brought me into McDonald's and he was a patient and helpful mentor," Kempczinski said, thanking him for his contributions.
- With AP