Panetta joined the Bank of Italy's Research Department in 1985,[6] becoming Head of its Monetary and Financial Division in 1999. From 2007 to 2011 he headed the Economic Outlook and Monetary Policy Department. In July 2011 he became Managing Director with the task of coordinating the Bank's activities relating to the Eurosystem.[7] From 2010 to 2012 he was director in charge of the Financial Stability Report.
From 8 October 2012 to 9 May 2019 Panetta served as Deputy Director-General of the Bank of Italy, and immediately after he became Senior Deputy Governor of the Bank of Italy (Presidential Decree of 3 May 2019).[7] He has held important positions and represented the Bank of Italy in numerous European and international institutions, including the OECD, the IMF, the G10, the ECB and the BIS.[8] He is also a member of the directorate of the Bank of Italy and of the Institute for Insurance Supervision as well as a member of the board of directors of the Bank for International Settlements and substitute for the Governor on the ECB's Governing Council. He is also a member of the ECB Supervisory Board, which took over European Banking Supervision on 4 November 2014.
From 1 January 2020 onward Panetta has been an Executive Board member at the European Central Bank, replacing the French Benoît Cœuré. He is responsible for the directorates dealing with International and European relations, with market infrastructure, payments and banknotes.[9][8]
Panetta has a reputation among his colleagues for his staunch defense of Italian banking systems and an opponent of bail-in-rules.[6]