She has performed in world premieres of several operas, such as Michael Daugherty's Jackie O (1997), Mark Adamo's Little Women (1999/2000), Jake Heggie's Great Scott (2015), and Kevin Puts's The Hours (2022).
She became interested in opera after seeing a PBS telecast of Don Giovanni,[3] and then, in her junior year, when she was cast in a school production of Die Fledermaus.
[4] Following her studies in Philadelphia, she was accepted in the Santa Fe Opera's Apprentice Singer program for the summer 1995 festival season, where she appeared in several minor roles and understudied for larger parts in such operas as Mozart's The Marriage of Figaro, Richard Strauss' Salome, Kálmán's Gräfin Mariza and the 1994 world premiere of David Lang's Modern Painters.
[7] In a 2016 interview with English mezzo-soprano Janet Baker, DiDonato discussed that from age 26 to 29 (circa 1995–1998), she radically changed her vocal technique.
She most notably appeared as the main heroine, Maslova, in the world premiere of Tod Machover's Resurrection with Houston Grand Opera.
Also at Houston Grand Opera, she performed the role of Meg in the world premiere during the 1999/2000 season of Mark Adamo's Little Women with Stephanie Novacek as Jo and Chad Shelton as Laurie.
She gave a recital at New York's Morgan Library under the auspices of the George London Foundation and featured as a soloist in the Seattle Symphony production of Handel's Messiah.
[citation needed] The 2002/03 season saw debuts with the New York City Opera as Sister Helen in Jake Heggie's Dead Man Walking, at the Théâtre du Châtelet in the title role of La Cenerentola, at the Royal Opera House as Zlatohřbítek the fox in Janáček's The Cunning Little Vixen under Sir John Eliot Gardiner, and with the New National Theatre Tokyo as Rosina in The Barber of Seville.
In concert, she performed Mozart's Requiem with the Seattle Symphony, Berlioz's Les nuits d'été with the Ensemble Orchestral de Paris, and made her Carnegie Hall debut in a production of Bach's Mass in B Minor with the Orchestra of St. Luke's under the baton of Peter Schreier.
[10] During the 2005/06 season, she made her Metropolitan Opera debut as Cherubino in The Marriage of Figaro and also played Stéphano in Gounod's Roméo et Juliette there.
She also sang Roméo in Bellini's I Capuleti e i Montecchi at the Opéra Bastille and returned to Teatro Real as Idamante in Idomeneo in July 2008.
She gave recitals at La Scala, Lincoln Center, and the Brooklyn Academy of Music, and performed a special concert of Handel arias which was recorded in Brussels.
[citation needed] She also appeared in concerts with the New York Philharmonic, Kansas City Symphony, and the Metropolitan Opera Orchestra, the latter of which under the baton of James Levine.
She toured Europe and the United States with Les Talens Lyriques, giving concerts of Handel arias, including performances at Wigmore Hall and the Rossini Opera Festival.
[18] For the first time in its 57-year history, the Santa Fe Opera added an extra performance of La donna del lago due to unprecedented ticket demand.
as well as "You'll Never Walk Alone" from the musical Carousel, "Over the Rainbow" from the Wizard of Oz as a bow to her home State of Kansas, and "Danny Boy"; she then led the audience into the traditional "Rule, Britannia!".
[20] On September 21, 2013, she sang the role of Romeo as the Lyric Opera of Kansas City opened its season with Bellini's I Capuleti e i Montecchi.
[32] This is a three-day program where several aspiring singers (usually college students) study with her personally over three days, to receive important feedback regarding their performance and vocal abilities.
[35] The project, which lasted for three years, also toured to Russia, Asia, and South America; the 4 June 2017 performance at the Liceu was filmed and later released on DVD.
The last performances in November 2019 staged at the Kennedy Center, Washington D.C. was followed by a conversation with Donna Leon and Justice Ruth Bader Ginsburg.