During her studies, she worked with Jolanda Magnoni, Rodolfo Celletti, and Elisabeth Schwarzkopf. After graduating she won the Voci Rossiniane competition in Milan and it launched her international career.

Under conductor Thomas Schippers she sang the role of Mimì in Puccini’s “La Bohème” in Cincinnati and was later invited by Luchino Visconti to appear in Verdi’s “Don Carlos” at the Teatro dell’Opera di Roma.

From there she appeared at the Maggio Musicale Fiorentino as Violetta in Verdi’s La Traviata, a role she sang over 200 times.

In 1978, Nicolesco made her debut at the Metropolitan Opera and went on to perform at many of the leading theaters in the world including Teatro alla Scala, Salzburg Festival, and Rossini Opera Festival.

Among the operas she performed included the world première of Luciano Berio’s “La Vera Storia,” Donna Anna in Dargomyzhsky’s “The Stone Guest,” Cinna in Mozart’s “Lucio Silla,” the soprano solo of Penderecki’s Polish Requiem, Euridice in Rossi’s “Orfeo, La Protagonista in Berio’s “Un re in ascolto,” and Queen Climene in Jommelli’s “Fetonte.”

She also interpreted works from Baroque, bel canto, verismo, and contemporary music. Among the roles from this period Marzelline in Beethoven’s “Fidelio,” Mozart’s Elettra in “Idomeneo” and Vitellia in “La Clemenza di Tito,” the title roles of Bellini’s “Beatrice di Tenda,” Donizetti’s” Anna Bolena,” “Maria di Rohan” and “Maria Stuarda,” Queen Elizabeth I in “Roberto Devereux,” Verdi’s Luisa in “Luisa Miller,” Amelia in “Simon Boccanegra,” Leonora in “Il Trovatore” and Desdemona in “Otello.”

In 1991 Nicolesco returned to Romania after the fall of the Communist regime and sang in the country for the first time on a stage in her native country. She went on to create the Romanian Atheneum International Foundation and donated in 1994 a Steinway grand concert piano.

She also initiated the Hariclea Darclée International Voice Competition and Festival and created the Romanian National Festival and Song Competition.

Among the many honors of her storied included being an honorary member of the Romanian Academy, Officer of the Order of the Arts and Letters in France, and an honorary doctor of the Gheorghe Dima Music Academy in Cluj-Napoca. She was also awarded the Order of the Star of Italian Solidarity, the Order of the Star of Romania, and was named UNESCO Artist for Peace and UNESCO Goodwill Ambassador. She was elected the Most Successful Woman in Romania and was conferred the Special Award Kulturpreis Europa Medal in Sibiu, European Capital of Culture in 2007, among many others.