Born in Los Angeles to Lebanese parents, Kayyem graduated from Harvard University with her bachelor’s degree in 1991 and from Harvard Law School with a Juris Doctor degree in 1995.

A lawyer by training, she began her legal career in 1995 at the Department of Justice, ultimately serving as an advisor to then Attorney General Janet Reno until 1999.

Since 2001, Kayyem has been a resident scholar at the Belfer Center, serving both as Executive Director of the Kennedy School’s Executive Session on Domestic Preparedness, a terrorism and homeland security research program, and as co-Director of Harvard’s Long-Term Legal Strategy for Combating Terrorism. She also taught courses on law and national security.

She was appointed as Massachusetts’ first Undersecretary for Homeland Security by Governor Deval L. Patrick in January 2007, overseeing the National Guard, the commonwealth’s strategic security planning, and the distribution of homeland security funds consistent with the Governor’s priorities.

On March 5, 2009 United States Department of Homeland Security Secretary Janet Napolitano appointed Juliette N. Kayyem Assistant Secretary for Intergovernmental Affairs. As Assistant Secretary, Kayyem was responsible for coordinated and consistent planning between the Department and all of its state, local, tribal, and territorial partners on issues as varied as immigration, intelligence sharing, military affairs, border security, and the response to operational events such as H1N1 influenza outbreak, the December 25th attempted terrorist attack, the Haiti earthquake, and the BP oil spill. In this capacity, she also served as the co-chair of congressionally mandated Preparedness Task Force and a member of President Obama’s Task Force on Puerto Rico and the Defense Department’s Council of Governors. She also managed the security efforts surrounding major sporting events, including the Chicago Olympic bid, the Vancouver Olympics, the Caribbean Games, and the World Equestrian Games. She was the most senior Arab-American female appointee in the Obama Administration. She left the DHS in the fall of 2010. On May 7, 2015, United States Department of Homeland Security Secretary Jeh Johnson appointed Kayyem to the Homeland Security Advisory Committee.

On August 21, 2013, Kayyem announced she was running for Governor of Massachusetts.

In February 2014, it was reported by The Boston Globe that Kayyem failed to vote in either 2009 and 2010. At the time she was living temporarily in Washington, D.C., and did not ask for an absentee ballot for Massachusetts or register to vote in the District of Columbia.

At the state party convention on June 14, 2014, Kayyem failed to receive the 15% of delegate votes required to make the primary ballot.

In October 2017, Kayyem became the chief executive officer of Massachusetts-based Zemcar, an on-demand and scheduled ridesharing company focused on children and seniors. Zemcar discontinued its rideshare services in December 2018.

After ending operations in December 2018, it was announced in March 2019 that Kayyem is chief executive officer of Grip Mobility – a technology company focused on providing transparency in the rideshare industry.

Kayyem serves as a senior advisor to NSO Group, an Israeli technology firm known for its Pegasus spying tool. The company has been reported to provide spying software that has been used in targeted attacks against human rights activists and journalists in various countries, and played a role in the murder of Saudi dissident Jamal Khashoggi. On October 21, 2019, Kayyem was hired as an opinion contributor by the Washington Post, where Khashoggi worked as a columnist. Observers pointed out the problematic nature of the hire. The director of Citizen Lab, a laboratory that studies human rights abuses and technology told Forbes at the time: “It is a sad day for human rights, a deeply disturbing irony in the wake of Khashoggi’s execution, and a public relations victory for NSO Group, to have the Washington Post hire someone sitting on their advisory board.” Facing mounting criticism, Kayyem stepped down from her Washington Post role just four days later, issuing a tweet that didn’t clarify her role at NSO Group.