From a young age Domenico wanted to become an actor. After his military service he enrolled in an acting school, later appearing in a few films. After staring in Il Mantello Rosso he became a singer.

He became very popular in the United States in the 1950s. His 1958 Eurovision Song Contest entry, "Nel blu Dipinto di blu" became a success in the United States. In 1960 he was accused of plagiarising an opera composer's song, but was found not guilty.