Uber said Gautam Gupta, its head of strategic finance, will be in charge of its finances while it looks for a permanent replacement. It said Callinicos will continue to advise Uber.
The San Francisco company announced Callinicos' departure in an email from CEO Travis Kalanick.
In an email to Uber employees, Callinicos said he has worked nonstop since receiving his MBA 26 years ago and wants to spend more time with his wife and daughter. Uber hired Callinicos in September 2013. He worked at Google for seven years and was treasurer and chief accountant before joining Uber. He also worked for Microsoft for 14 years.
Uber is a taxi alternative company that lets passengers summon cars through an app, linking would-be riders directly to nearby drivers. It operates in more than 50 countries and is valued at $40 billion. However it faces a variety of legal and regulatory challenges as it expands.
The company has been criticized for the thoroughness of its background checks on drivers and other safety issues, as well as its method of raising prices when demand goes up.
The AP contributed to this report.