[3][4] He was born in Richmond, Virginia, and raised in Iran, Mostashari moved to upstate New York at age 14.

He then joined the New York City Department of Health, where he launched the primary care information project under Thomas Frieden.

The project focused on accelerating the adoption of electronic health record systems as a means of improving primary care quality in New York City.

Following the passage of the HITECH act, David Blumenthal recruited Mostashari to serve as deputy national coordinator for health information technology in July 2009 and eventually succeeded him as national coordinator on 8 April 2011.

In August 2013, he announced his resignation,[8] and following his departure, became a visiting fellow at the Brookings Institution's Engelberg Center for Health Care Reform.