Gigli studied in Rome, and, after winning a competition at Parma in 1914, he made his debut at Rovigo, Italy, as Enzo in Amilcare Ponchielli's La gioconda. Following engagements in Spain and South America, he made his debut at the Metropolitan Opera in New York City (1920) as Faust in Arrigo Boito's Mefistofele. He remained with the company for 12 seasons. Gigli first appeared in London in 1930 at Covent Garden in Umberto Giordano's Andrea Chenier. Between 1935 and 1951 he made numerous films in Germany and Italy.

His lyric tenor voice was remarkable for its power, mellowness, and smoothness of production. Although his musical taste had flaws and his acting was somewhat stiff, his natural musicianship and the charm of his voice held operatic audiences. From 1946 he often appeared in opera with his daughter, the soprano Rina Gigli. His last operatic appearance was in 1954, his last concert in 1955.