Nagl studied mathematics and physics at Friedrich Alexander University in Erlangen (FAU). After two years in industry at the research center of Siemens AG in Erlangen, he returned to the Institute of Computer Science at FAU and received his PhD in 1974 from the chair of Hans-Jürgen Schneider on Graph - Grammars.
After his Habilitation in 1978 at the Technical Faculty of FAU, he accepted a C3 professorship at the University of Koblenz in 1979 and a C4 professorship at the University of Osnabrück in 1981. In 1986 he became holder of the chair of computer science 3 (software engineering) at the RWTH Aachen. He declined a call in 1992 to the University of Zurich. In August 2009 he retired and handed over the chair of Computer Science 3 to Bernhard Rumpe.
From 1990 to 1997 he was spokesperson of the DFG research group SUKITS, from 1997 to 2006 spokesperson of the Collaborative Research Center 476, and from 2006 to 2009 spokesperson of the DFG’s Transfer Area 61. A considerable number of his former collaborators are professors.
Manfred Nagl was chairman of the Fakultätentag Informatik from 2006 to 2008 (vice chairman from 2009 to 2011), and chairman of the umbrella association 4ING /Fakultätentage der Ingenieurwissenschaften und der Informatik an Universitäten e. V./ from 2007 to 2008 (09 - 11 member of the steering committee). From 2005 to 2007 he was and since 2011 he is a member of the board of Informatics Europe, a kind of European Faculty Association of Informatics. There he leads a commission for the evaluation of computer science faculties. In EQANIE (European Informatics Accreditation) he is vice-chair of the accreditation commission.
In 2009 he was appointed Fellow of the Gesellschaft für Informatik. On November 26, 2010, he was awarded an honorary doctorate (Dr. rer. nat. h. c.) by the Faculty of Electrical Engineering, Computer Science and Mathematics of the University of Paderborn.