In 1994, she graduated from Rhinebeck High School. During high school Mastromonaco worked in various jobs, including her first job as a checkout person at a grocery store called Kilmer’s IGA.

Mastromonaco went to the University of Vermont for two years, majoring in French with a minor in Japanese. She then transferred to the University of Wisconsin-Madison, where she graduated with a Bachelor of Arts in political science in 1998.

In 2000, Mastromonaco moved to Boston and got her first job in politics as a staff assistant to Senator John Kerry. For a short time, after 9/11, she worked at a Republican lobbyist group, Richard Berman’s American Beverage Institute, as director of membership. In 2002, Mastromonaco was hired as Press Secretary for Congressman Rick Boucher of Virginia, but in December 2002 went back to work for Kerry. In 2004, Mastromonaco was hired as the Director of Scheduling for Senator Kerry’s presidential campaign.

Starting in February 2004, Mastromonaco joined the then Illinois State Senator Barack Obama’s campaign during his run for United States Senate. She was hired as Director of Scheduling. The team who made up that office included Jon Favreau, Tommy Vietor, Robert Gibbs, and Pete Rouse.

From 2007 to 2008, Mastromonaco was Political Director for Obama’s Political Action Committee (PAC), Hopefund, during the 2006 midterm elections. The mission of the PAC was to teach young people who had no experience in the political process how to be field and community organizers. Following Obama’s announcement in February 2007, Mastromonaco served as Director of Scheduling and Advance for Barack Obama’s presidential campaign.

In November 2008, Mastromonaco was appointed Director of Scheduling and Advance in the administration of President Barack Obama.

In January 2011, she was appointed Deputy Chief of Staff for Operations. In November 2011, The New Republic magazine listed Mastromonaco on its “2011 List Issue” as being one of Washington’s most powerful, least famous people. Along with Nancy-Ann DeParle, who was White House Deputy Chief of Staff for Policy, it was the first time a presidential administration had two women deputies in power. She was notable for her long institutional memory, the ability to understand logistics, and her low-key approach to the position.

In November 2013, Mastromonaco married David Krone, who had worked with Senate Minority Leader Harry Reid and was his Chief of Staff from 2008 to 2015. They were married by Justice Elena Kagan at the Supreme Court. The couple currently lives in the Tribeca neighborhood of New York City.

In May 2014, Mastromonaco left her position as Deputy Chief of Staff for Operations. She was replaced by Anita Decker Breckenridge.

In June 2014, Mastromonaco was hired as a contributing editor at Marie Claire. In January 2015, Mastromonaco joined Vice Media as Chief Operating Officer.

Mastromonaco’s first book, Who Thought This Was a Good Idea? And Other Questions You Should Have Answers to When You Work in the White House, was published by Twelve in March 2017.

Since October 2017 Mastromonaco is a Contributor to Crooked Media and frequent guest on Crooked Media podcasts.