Born in Quartieri Spagnoli, Naples, Gragnaniello began playing the guitar at the age of 12 and began composing his first songs at 18 years old. In 1977 he formed the group "Banchi nuovi", named after the Committee of unemployed people to which he belonged. Gragnaniello made his solo debut in 1983, with the eponymous album Enzo Gragnaniello.
In 1999 he entered the competition at the Sanremo Music Festival in a duet with Ornella Vanoni, ranking fourth with the song "Alberi".
Gragnaniello composed songs for Andrea Bocelli, Adriano Celentano, Gerardina Trovato among others He is also active as a composer of musical scores for stage plays and films.