Specializing in 19th-century Italian opera, Radvanovsky is widely regarded as a leading interpreter of bel canto, verismo, and works by Giuseppe Verdi.

Her repertoire includes the title roles in Médée, Norma, Tosca, and Rusalka, Leonora in Il trovatore, Lady Macbeth in Macbeth, and Donizetti's "Tudor Queens": the title roles in Anna Bolena, Maria Stuarda, and Elizabeth I in Roberto Devereux.

[5] In 1995 Radvanovsky won the Metropolitan Opera National Council Auditions[6] and first prize in the Loren L. Zachary Society Competition.

[8] After the National Council Auditions, Radvanovsky enrolled in the Metropolitan Opera's Lindemann Young Artist Development Program.

[12] In 2006, she made her debut at the Royal Opera House in London in Alfano's Cyrano de Bergerac, opposite Plácido Domingo in the title role.

[21] On 4 July 2018, she repeated the aria D'amor sull'ali rosee during a performance of Il trovatore at the Opéra Bastille in Paris, the first woman - and only the third singer - to sing an encore since the house's opening in 1989.

For the 2022-2023 season at the Metropolitan Opera, Radvanovsky sang the title role in the company's first-ever new production of Cherubini's Médée.

[22] During the COVID-19 pandemic, Radvanovsky and fellow soprano Keri Alkema launched a podcast series entitled Screaming Divas with the first episode aired on 24 April 2020.

[34] She won "Outstanding Female Performance" in the 2017 Dora Award for Norma with Canadian Opera Company.