Nathalie Dessaix was born in Lyon, she was raised in Saint-Médard-en-Jalles, where she had a few singing lessons with madame Saintrais, a former chorister at the Bordeaux Opera.

In 1988, she won the first edition of competition "Voix Nouvelles",[a] run by France Télécom and was granted a year's study at the "École d'art lyrique" of the Paris Opera, where she sang Elisa in Mozart's Il re pastore.

[10] Dessay was quickly approached by a number of regional theatres, and engaged in roles such as Blonde (Die Entführung aus dem Serail), Madame Herz (Der Schauspieldirektor), Zerbinetta (Ariadne auf Naxos).

In April 1992 she made her Paris Opera debut, singing the role of Olympia in The Tales of Hoffmann with José van Dam.

After attending a performance where Barbara Bonney had sung Sophie in Der Rosenkavalier under Carlos Kleiber, she was cast in the same role with another conductor.

Besides Olympia, Blonde, Zerbinetta, her best known and most often played roles, she also performed Italian Singer (Capriccio), Aminta (Die schweigsame Frau), Fiakermilli (Arabella) with the company.

[11] Dessay sang her first Queen of the Night in The Magic Flute at the 1994 Aix-en-Provence Festival in Robert Carsen's staging to critical acclaim.

[19][20] In 1997 she sang the title role in Stravinsky's The Nightingale conducted by Pierre Boulez and staged by Stanislas Nordey at the Théâtre du Châtelet.

In 1998 she portrayed Olympia at the Met,[23] and later in the year in Lyon, performed Tytania in Britten's A Midsummer Night's Dream and Aspasia in Mozart's Mitridate, re di Ponto.

[30] Later in the year, she took up the role of Konstanze in Die Entführung aus dem Serail at the Grand Théâtre de Genève,[31] and then interpreted the Queen of the Night for the last time at Palais Garnier, with her last performance on 24 December 2000.

[36] Subsequently, she was forced to cancel several other performances, including the French version of Lucia di Lammermoor in Lyon and a Zerbinetta at the Royal Opera House in London.

[37] She returned to the stage in March 2003 in Ariadne auf Naxos at the Met, and later in the year performed in the premiere of Laurent Pelly's new production of the opera at the Palais Garnier.

[50][51] The year 2007 saw Dessay starring in the premiere of Laurent Pelly's production of La fille du régiment at Covent Garden, and its reprise at the Vienna State Opera.

[52][53] She performed the title role in Manon at the Liceu in Barcelona in June/July and opened the season at the Metropolitan Opera in the new Mary Zimmerman production of Lucia di Lammermoor.

[58][59] She went on performing Lucia at the San Francisco Opera and a joint concert with tenor Jonas Kaufmann as part of the Festival de Radio France et Montpellier.

[63][64] On 2 March 2009, Dessay premiered in Zimmerman's new production of La sonnambula opposite Juan Diego Flórez at the New York Metropolitan Opera.

[71] She performed in a joint concert with Juan Diego Flórez at the Chorégies d'Orange,[72] before going on Teatro Regio di Torino's Japan tour of La traviata.

In January 2012, Dessay starred in the premiere of Coline Serreau's production of Massenet's Manon in the title role at the Opéra Bastille.

[81] She returned to the Met in April for Willy Decker's production of La traviata, where she was replaced by Hong Hei-kyung on the opening night and, in another performance, after the first act, due to a cold.

[82][83] She was originally going to portray all main heroines in The Tales of Hoffmann at the Salle Pleyel, yet she withdrew for unspecified reasons and was replaced by Sonya Yoncheva.

[86] In June 2013, Dessay announced that the title role of Massenet's Manon at the Théâtre du Capitole in Toulouse on 15 October 2013 would be her final operatic performance.

[92] Dessay made her theatre debut in May 2015 in a French adaption of Howard Barker's monologue Und, staged by Jacques Vincey, at the Théâtre Olympia in Tours.