From 1993 to 1995, Shapiro served as a professional staff member on the House Foreign Affairs Committee under Chairman Lee H. Hamilton. From 1995 to 1999, he was a legislative assistant and senior foreign policy adviser to Senator Dianne Feinstein. From 1999 to 2001, he sat on the National Security Council under President Bill Clinton, as director of legislative affairs, and as a Congressional liaison for National Security AdviserSandy Berger. From 2001 to 2007, he was first legislative adviser and then deputy chief of staff (primarily on foreign policy issues) for U.S. Senator Bill Nelson. From 2007 to 2008, he was vice president of the Washington, D.C., lobbying firm Timmons & Company.[13]
Shapiro had served as an advisor to then-U.S. Sen. Barack Obama on Middle East and Jewish community issues since 2007, also assisting as strategist and fundraiser.[14] He accompanied Obama on his July 2008 trip to Israel; in August 2008, Obama appointed him senior policy adviser and Jewish outreach coordinator for his 2008 presidential campaign.[15]
In January 2009, Shapiro was appointed senior director for the Middle East and North Africa of the U.S. National Security Council. Focusing on Israel, he attended every Israel-related meeting, and met with every senior Israeli diplomat and military officer who visited Washington, D.C. Shapiro often accompanied U.S. Special Envoy for Middle East Peace George J. Mitchell on his trips to the region, and played a central role in talks regarding the Middle East Peace Process and the strengthening of military cooperation between the U.S. and Israel. He maintained close relations with Benyamin Netanyahu, in spite of tensions between the Israeli prime minister and President Obama.[16] In June 2011, he was appointed Ambassador to Israel. Shapiro took leave of the President of Israel, Reuven Rivlin, on January 17, 2017 before holding his final meeting with Netanyahu two days later, which one newspaper described as a "terse farewell."[17]