Nuccia Focile was born in Sicily, studied in Turin under Elio Battaglia, and made her opera debut in 1983 as Serpina in La Serva Padrona by Pergolesi in Spoleto. In 1984 she sang her first Mimi in La Boheme by Puccini at the Teatro Regio in Turin and made her debut as Oscar in Verdi's Un ballo in maschera at La Scala in 1986. Also in that year, she won the International Pavarotti Competition in Philadelphia, following which she made many concert appearances with the famous tenor. In 1995 she made her Metropolitan Opera debut as Mimì in Puccini's La bohème.
Nuccia Focile has appeared in many roles, such as Nannetta in Falstaff by Verdi, Nedda in Pagliacci, Violetta in La Traviata, Elisabeth in Verdi's Don Carlos, Susanna in Le Nozze di Figaro, the title role in Madama Butterfly and Katya Kabanova, Tatiana in Eugene Onegin, Amelia in Simon Boccanegra, the title role in Jenufa for the Welsh National Opera, Despina in Mozart's Così fan tutte for both the Metropolitan Opera and Lyric Opera of Chicago, Adina in Donizetti's L'elisir d'amore for Opéra de Monte-Carlo, Mimì for Teatro Comunale di Bologna and Seattle Opera, and Musetta (also in La bohème) for Royal Opera, London.
She brings an "almost unbearable poignancy"  to Mimì, her best-known role. Her other roles include Donna Elvira in Don Giovanni, the title role in Gluck's Iphigenia in Tauris, Nedda in Leoncavallo's Pagliacci, Alice Ford in Verdi's Falstaff, the Countess in Mozart's Le nozze di Figaro, the title role in Menotti's Maria Golovin, Desdemona in Verdi's Otello, Violetta in Verdi's La traviata, and Tatyana in Tchaikovsky's Eugene Onegin which she recorded for Philips.
She has made several recordings for the Philips, Opera Rara and Telarc labels, including three Mozart operas (Le Nozze di Figaro, Così fan tutte and Don Giovanni) conducted by Sir Charles Mackerras.
She lives near Cardiff, Wales, with her daughter.