He studied in Florence with Titta Ruffo and Riccardo Stracciari and made his debut there in 1937, as Giorgio Germont in La traviata, and also sang at the premiere of Gian Francesco Malipiero's Antonio e Cleopatra, in 1938.
He appeared in two legendary performances opposite Maria Callas, the first at the Maggio Musicale Fiorentino in 1951, as Montforte in I vespri siciliani, under Erich Kleiber, and on opening night of the 1952-53 season at La Scala, as Macbeth, under Victor de Sabata.
After the war, he began an international career, appearing in Paris, Vienna, Prague, London, Mexico City, Rio de Janeiro, Chicago, San Francisco, etc.
In 1946 and 1947, Mascherini appeared at the New York City Opera, in La bohème (as Marcello), La traviata (with Dorothy Kirsten), Pagliacci (as Silvio, later as Tonio), Rigoletto, Andrea Chénier (opposite Vivian della Chiesa, directed by Theodore Komisarjevsky), and Il barbiere di Siviglia (with Luigi Infantino and Virginia MacWatters).
He made his debut at the Metropolitan Opera on 7 December 1949 as Marcello in Giacomo Puccini's La bohème with Bidu Sayão as Mimì, Ferruccio Tagliavini as Rodolfo, Lois Hunt as Musetta, and Giuseppe Antonicelli conducting.