[1] Wolfsthal graduated from the New Lincoln School in Manhattan and earned a Bachelor of Arts degree in Political Science from Emory University in 1988.

[6] From 2014 to 2017, Wolfsthal served as a special assistant to President Barack Obama and Senior Director for Arms Control and Nonproliferation on the United States National Security Council.

He was involved in crafting President Obama's Prague speech delivered in April 2009, served on the delegation to the 2010 Nuclear Security Summit, helped negotiate and gain Senate approval of the New START arms control agreement with Russia, helped draft the 2010 Nuclear Posture Review[9] and coordinated U.S. policy for the 2015 NPT Review Conference.

[10][11] The co-author of Deadly Arsenals: Tracking Weapons of Mass Destruction, he was described by the office of U.S. Vice President Joe Biden as "a globally recognized expert on nuclear security and nonproliferation",[6] He served previously as deputy director of the James C. Martin Center for Nonproliferation Studies at the Middlebury Institute of International Security at Monterey.

[17] Project Atom 2023: A Competitive Strategies Approach for U.S. Nuclear Posture through 2035, Center for Strategic and International Studies, September 30, 2023 (co-authored with Heather Williams, Kelsey Hartigan, Lachlan MacKenzie, Robert Soofer, Tom Karako, Franklin Miller, Leonor Tomero, and Oriana Skylar Mastro)[18] Wolfsthal is married to Shanthi Kalathil.