In Naples he received a classical education at the Liceo Umberto and, in 1977, took his undergraduate degree in law, with honors, from the Università degli Studi of Naples. Selected each time through the competitive state exam process, he became an Ordinary Judge in 1979, Legal Secretary of the Regional Administrative Court in 1984, and a State Attorney in 1985. In 2009 he was appointed Division President. Within the Council of State, he has held various roles in all the judicial and advisory divisions.

After serving as Assistant President, President of the Fourth Division, and Director of the Ufficio Studi Massimario e Formazione della Giustizia Amministrativa, he was appointed President of the Council of State by decree of the President of the Republic on 25 September 2018.

On 15 December 2021, Judge Patroni Griffi was elected to the Constitutional Court by his colleagues on the Council of State, replacing outgoing President Giancarlo Coraggio. He was sworn in by the President of the Republic on 29 January 2022.

Judge Patroni Griffi was a member of the Committee that drafted the Code of Administrative Procedure.

He has been invited to speak many times at meetings of the Supreme Courts and Councils of States of the European Union and at the OSCE.

He was first Vice President, and later President, starting his tenure in September 2018, of ACA-Europe, the Association of Councils of State and Supreme Administrative Councils.

He is a member of the scholarly boards of several law journals and the author of published works in the fields of public sector organization, the prevention of corruption, administrative justice, sources of law, and regulatory quality.

He served as Minister of Public Administration in the Monti Government and Undersecretary of the Office of the President of the Council in the Letta Government.

In the past, Judge Patroni Griffi has served in the positions of Coordinator of the Unit for Simplifying Rules and Procedures, Cabinet Head for Legal and Legislative Affairs for the Office of the President of the Council in the Prodi Government, Secretary General of the Personal Data Protection Authority, and member of the Independent Committee for Evaluating Transparency (Civit). He was Head of the Cabinet of Ministers under Amato (Minister of Institutional Reforms) and Brunetta (Minister of the Public Domain) and Head of the Legislative Office of Ministers of the Public Domain Cassese, Frattini, Motzo, and Bassanini.

He served as President of the Teatro di Napoli – Teatro Nazionale theater.

He was Vice President of SVIMEZ, Associazione per lo Sviluppo del Mezzogiorno.

He holds the title of Cavaliere di Gran Croce of the Italian Republic.

He was awarded the Sele d’Oro Mezzogiorno in 2013.

He was awarded the Sandulli prize in 2019.

He was awarded the international Guido Dorso prize in 2020.