Leonard was born in New York City. For five years she sang with the Manhattan School of Music children's chorus. She attended the Joffrey Ballet School. She is a graduate of The Cathedral School of St. John the Divine and the Fiorello H. LaGuardia High School of Music & Art and Performing Arts. She earned her Bachelor of Music and Master of Music degrees at the Juilliard School, where she was a pupil of Edith Bers. She has also studied with Marilyn Horne, Brian Zeger, Warren Jones, and Margo Garrett. She is a 2005 winner of a Marilyn Horne Foundation award. In 2006, she received The Licia Albanese-Puccini Foundation Award. She was also chosen as a recipient of a Movado Future Legends award in 2006. In 2013, she received the Richard Tucker Music Foundation Award.
In New York, Leonard has performed with the Chamber Music Society of Lincoln Center and with the Juilliard Opera Center. Her first appearance with the New York Philharmonic was in a concert version of Leonard Bernstein's Candide, and she later sang the part of the Squirrel in L'enfant et les sortilèges in concert with the orchestra and Lorin Maazel. In February 2007, Leonard made her professional operatic stage debut as Stéphano in Roméo et Juliette. In September 2007, she made her Metropolitan Opera debut in the same role. Leonard made her debut with Santa Fe Opera as Cherubino in 2008. Her commercial recordings include a DVD recording for Euroarts as Dorabella in the 2009 Salzburg Festival production of Così fan tutte. On April 26, 2014, Leonard sang the role of Dorabella in a performance at the Metropolitan Opera that was transmitted worldwide as part of the Metropolitan Opera Live in HD program. In February 2011, Leonard made her Vienna State Opera debut singing Cherubino in Le nozze di Figaro, returning to the venue in January 2012 as Rosina in Il barbiere di Siviglia. 2014 to 2016 Leonard and Sharon Isbin performed a well-received series of eleven soprano/guitar-duet recitals, including at Zankel Hall (Carnegie Hall).
- Trish Hall (January 26, 1989). "Child Care, as Seen by Children". The New York Times. Retrieved 2008-02-07.
- Rowat, Robert (January 31, 2013). "Isabel Leonard, opera's new 'it girl'". CBC Music. Archived from the original on March 1, 2016. Retrieved 2016-02-18.
- Driscoll, F. Paul (March 2008). "Sound Bites: Isabel Leonard". Opera News. 72 (9). Retrieved 2010-11-20.
- Kathryn Shattuck (2010-11-12). "It's Not Over Till the Svelte Mama Sings". The New York Times. Retrieved 2016-08-16.
- Jeremy Eichler (15 November 2005). "A Mozart Clan: Nice Sounds Veiled by One Celestial Note". The New York Times. Retrieved 2008-02-07.
- Bernard Holland (18 November 2006). "A U.P.S. Man Joins Offenbach's Gods and Goddesses". The New York Times. Retrieved 2008-02-07.
- Anthony Tommasini (7 October 2006). "Childhood Fantasies, Without All the Cutesy". The New York Times. Retrieved 2008-02-07.
- Anne Midgette (27 September 2007). "The Lovers of Verona, Swaggering and Soaring". The New York Times. Retrieved 2008-02-07.
- Anthony Tommasini (4 August 2008). "From Handel, Faithlessness and Devotion". The New York Times. Retrieved 2008-08-16.
- Opera Today review of Euroarts DVD of Così fan tutte
- Brookes, Stephen (March 25, 2015). "Mezzo-soprano Isabel Leonard shines with guitarist Sharon Isbin". The Washington Post. Retrieved 2016-08-20.
- Schweitzer, Vivien (November 13, 2015). "Isabel Leonard and Sharon Isbin in a Duet of Voice and Guitar". The New York Times. Retrieved 2016-08-20.
- Tischler, Gary (2018-04-19). "Isabel Leonard WNOs Rosina". Georgetowner. Retrieved 2018-04-19.