In 1953 the family moved to Milan and then returned to Rome, in the Talenti neighbourhood, where Epifani finished secondary school at a Liceo classico, obtaining a classical education diploma in 1969.

In 1973 he graduated from the Sapienza University of Rome in Philosophy with a thesis on Anna Kuliscioff and subsequently enrolled in the CGIL, where he worked as a trade unionist.

In 1979 he began his career as a union leader with the post of Secretary-General of the category of Printing and paper manufacturers.

On 16 October 2010 Guglielmo Epifani delivered his last speech as secretary of the CGIL in Piazza San Giovanni in Rome, on the occasion of the event FIOM.

[2] Epifani was re-elected to the Chamber of Deputies in the 2018 Italian general election, among the ranks of the Free and Equal list.