Spence spent seven years in senior national security positions in the Obama Administration. He has served as a foreign policy commentator on television, in the national news media — including the Washington Post, Los Angeles Times, and International Herald Tribune, in Congressional testimony, and in speeches and panels around the country.    

From 2012 to 2015, Spence served as Deputy Assistant Secretary of Defense for Middle East Policy, where he was the principal advisor to three Secretaries of Defense for U.S. policy towards the Middle East. He was responsible for 14 countries, including Iraq, Syria, Iran, Israel, Egypt, and the Gulf states.  During his time at the Pentagon, Spence traveled to the Middle East more than 30 times. He received the Secretary of Defense Award for Outstanding Public Service. From 2009 to 2012, Spence worked at the White House on the National Security Council as Special Assistant to the President and Senior Director for International Economic Affairs and as the Senior Advisor to two National Security Advisors. He also served on the Obama-Biden Presidential Transition Team.

Spence is the co-founder of and serves on the board of the Truman National Security Project. Trained as a lawyer, Spence also practiced criminal and international law in California, and served as a law clerk for Judge Richard Posner of the 7th Circuit Court of Appeals. A Marshall Scholar and Truman Scholar, Spence received his doctorate in International Relations from Oxford University; J.D. from Yale Law School; and B.A. and M.A. in International Policy Studies from Stanford University. He is also the William J. Perry Fellow at Stanford University, and a Senior Fellow at the Yale Law School Center on Global Legal Challenges and at the NYU Center on Law and Security. He is a member of the Council on Foreign Relations, the Advisory Group on the Foundation for the Defense of Democracies Project on Cyber-Enabled Economic Warfare, and  the City of San Jose Cybersecurity Innovation Council. He was born and raised in southern California.