His career began in the clubs of his hometown in late 1930s. In those years Turin's musical scene was very lively: Fred Buscaglione, for instance, was beginning his career performing in the city's nightclubs.

Thanks to Carlo Prato, who had earlier launched Trio Lescano, Ernesto Bonino had an audition at the Italian state radio company EIAR. He debuted on air on 5 January 1941 with the song Tango argentino. It was instant success. Other hits followed: La Paloma, Se fossi milionario, La famiglia canterina (with Trio Lescano), A zonzo, Musica Maestro, Il giovanotto matto, Ti comprerò l'armonica, Conosci mia cugina?. In 1940s Ernesto Bonino, dubbed "Mister Swing", rivalled only with Natalino Otto and Alberto Rabagliati in terms of popularity.

In 1947 he embarked on a long tour in Latin America: Peru, Argentina, Chile, Brazil, Venezuela, Mexico, Cuba. He and Tina de Mola took Havana by storm with their song Chinito chinita.

In 1952 he moved to the USA. His dream of singing jazz standards in the best clubs of New York, Chicago and Miami came true. He made a brief comeback to Italy in 1955 for the musical comedy La Granduchessa e i camerieri by Garinei and Giovannini. After that theater season was over, he went back to the US until 1958.

Ernesto Bonino took part only once to the San Remo Music Festival. It was in 1962 and he placed third with Gondolì, Gondolà, written by the duo Carosone-Nisa. After the contest, Carosone hired him for the European tour of his band.