Born in Castellammare del Golfo, Italy, Anton Guadagno studied at the Vincenzo Bellini Conservatory in Palermo and the Accademia di Santa Cecilia in Rome.
He worked with Herbert von Karajan while studying at the Salzburg Mozarteum, and won first prize for conducting in 1948 at the age of 25.
Upon graduation, he conducted in South America and Mexico City, where he was music director of the Bellas Artes and formed a lasting relationship with Plácido Domingo.
He made his American debut in 1952 at Carnegie Hall, and served as an assistant conductor at the Metropolitan Opera during the 1958–1959 season.
In 1984, Guadagno became principal conductor of the Palm Beach Opera, a position he held for the rest of his life.