Aprile Millo was born on April 14, 1958, in New York City. She was the daughter of Margherita Ghirosi and tenor Giovanni Millo, the first American hired by La Scala after World War II. She developed an early interest in music, and after graduating from high school in 1977, she was chosen to be one of the first eight apprentices at the San Diego Opera Center. A string of vocal awards followed, including the Geraldine Farrar Award, the Montserrat CaballÚ Award in Barcelona, and first prize in the Concorso Internazionale di Voci Verdiane in Bussetto, Italy.
Upon her return to the United States, Millo joined the Utah Opera Company in Salt Lake City. It was in Salt Lake City that she made her professional stage debut with the Utah Opera in the title role of Verdi's A´da in 1980. The following year, she travelled to New York to attend the Metropolitan Opera's open-call auditions, where she was invited to take part in the company's Young Artists Development Program. The next several years were spent learning roles, refining her acting style, and perfecting her vocal technique. During this time, she made her La Scala debut replacing Mirella Freni as Elvira in Ernani on January 4, 1983.
In 1984, Aprile Millo was signed to a three-year contract by the Met that called for her to work primarily as an understudy. On December 3, 1984, she made her Metropolitan debut replacing Anna Tomowa-Sintow as Amelia in Simon Boccanegra, which critics described as "a blazing success". Three weeks later, on December 22, she performed the same role in her originally scheduled Met debut. The next year, in 1985, Millo took first prize in the Richard Tucker Competition.
On January 19, 1986, Millo made her Carnegie Hall debut in a concert version of Verdi's I Lombardi alla prima Crociata. That year, she also achieved success in the role of A´da, singing the role in New York, as well as all over Europe and South America. It was as A´da that she opened the 1989-90 Met season in an Emmy-winning production that was also telecast internationally.
During her career, Millo has made several recordings, including a debut CD of Verdi arias called Presenting Aprile Millo which was released by Angel Records in 1986. She also recorded the singing voice for Elisabeth Taylor in Zeffirelli's film, "The Young Toscanini". She has an extensive Met repertoire, including the Verdi heroines she is famous for (including Desdemona, Luisa Miller, Leonora in Il Trovatore) as well as some Puccini roles, including Li¨ in Turandot and as Tosca, a role she sang at the Met in the 98/99 season.