She was inspired to become an opera singer after watching Zeffirelli's 1983 film of La traviata, which featured Plácido Domingo and Teresa Stratas.

In the next two years, she was engaged at the same theatre, featuring as Eliza Doolittle in My Fair Lady, and then as the Queen of the Night in Mozart's The Magic Flute, her debut in that role, and in the world premiere of Salieri's Cublai, gran kan de' Tartari (1998).

Since 2002, she embarked a freelance career, and had frequent engagements with the Bavarian State Opera in roles such as Adele in Die Fledermaus, Marzelline in Fidelio, and the Queen of the Night.

[7] Her engagements in Salzburg consist exclusively of roles in Mozart operas: The Magic Flute (Queen of the Night, 2002), Die Entführung aus dem Serail (Blonde, 2003; Konstanze, 2004), The Marriage of Figaro (Susanna, 2007).

[8][9] In the 2006 edition, which celebrated Mozart's 200th anniversary, she played the Queen of the Night in the premiere of Pierre Audi's production of The Magic Flute, and Fauno in Ascanio in Alba.

[10][11] Damrau made her Royal Opera, London debut in January 2003, in David McVicar's new production of The Magic Flute,[12] and then appeared in Arabella (Fiakermilli), Ariadne auf Naxos (Zerbinetta), and the world premiere of Maazel's 1984 in two consecutive seasons.

[16] In December 2004, she was invited to sing the title role in Salieri's Europa riconosciuta, conducted by Riccardo Muti, for the reopening of La Scala in Milan.

[17] In 2005, she portrayed Gilda in the premiere of Doris Dörrie's controversial production of Rigoletto in Munich,[18] and later in the year, made her Metropolitan Opera debut in New York City in the role of Zerbinetta.

[22] Since her debut in the 2005/06 season, she appeared in consecutive seasons at the Met, where she starred in new productions of The Barber of Seville (Rosina, 2006), Die ägyptische Helena (Aithra, 2007), and Rossini's comic opera Le comte Ory (Countess Adèle, 2011),[23] besides revivals of Die Enführung aus dem Serail, Lucia di Lammermoor (role debut as Lucia), La fille du régiment, Rigoletto, and L'elisir d'amore.

She performed alongside Plácido Domingo at the concert program "3 Orchester und Stars" in Munich to mark the opening of the 2006 FIFA World Cup.

She has performed with conductors as James Levine, Zubin Mehta, Lorin Maazel, Sir Colin Davis, Christoph von Dohnányi, Leonard Slatkin, Pierre Boulez, Nikolaus Harnoncourt and Jesús López Cobos.

[38][39] NB: * indicates a new production of the piece Early recordings include Verdi's canzoni, Mahler's Des Knaben Wunderhorn, and Schumann's Myrthen, Op.