Danièle Lebrun made her debut in Arthur Miller’s The Crucible (Les Sorcières de Salem) by Raymond Rouleau at the Théâtre Sarah-Bernhardt. Having won the first prize for acting at the Conservatoire, she was engaged by the Comédie-Française in 1958 and played in Bourdet’s The Weaker Sex (Le Sexe faible), Pirandello’s Right You Are (Chacun sa vérité) and Molière’s The Impromptu at Versailles (L’Impromptu de Versailles) and Les Précieuses ridicules. In 1960, she became part of the La Huchette Company and took part in Ionesco’s The Bald Soprano directed by Nicolas Bataille. From 1965, she collaborated with Antoine Bourseiller on Franz Kafka’s Amerika, Roger Planchon on Molière’s George Dandin and Alexandre Dumas’ The Three Musketeers (Les Trois Mousquetaires) and Laurent Terzieff on the creation of Slawomir Mrozek's Tango. For the opening of the Théâtre de la Ville in 1968, she played Beatrice in Shakespeare’s Much Ado About Nothing by Jorge Lavelli, Actor #1 in Pirandello’s Six Characters in Search of an Author (Six personnages en quête d’auteur) by Jean Mercure and Célimène in Molière’s Le Misanthrope by Marcel Bluwal. The following year, Pierre Debauche cast her as Regan in Shakespeare’s King Lear.

After Jacques Seiler entrusted her with the role of Madame in Christopher Frank’s La Mort de Lady Chatterley in 1971, Danièle Brun continued interpreting parts in works by contemporary authors including Raymond Queneau, Roland Dubillard and Robert Pinget. Jean Anouilh directed her in two of his own pieces: Ne réveillez pas Madame and Colombe, in which she played the title role_._ She has worked with many renowned directors, such as Alfredo Arias in Arthur Schnitzler's La Ronde, Gildas Bourdet in Marivaux's Les Fausses Confidences, Jérôme Savary in Oscar Wilde’s The Importance of Being Earnest, François Berreur in Lagarce’s Juste la fin du monde, Christophe Lidon in Chekhov’s The Seagull, Jean-Claude Brisville’s L’Antichambre and Eugène Ionesco's Délire à deux.

In 1976, she won the Critics Union Award for Mishima’s Madame de Sade directed by Jean-Pierre Granval. In 1992, she won the Molière Award for Best Supporting Actress for Molière’s Le Misanthrope by Francis Huster, and, in 2006, a second one for George Bernard Shaw’s Pygmalion by Nicolas Briançon.

Having rejoined the Comédie-Française for the second time in 2011, she played Dame Pluche in Musset’s No Trifling with Love (On ne badine pas avec l’amour) by Yves Beaunesne. Under the direction of Alain Françon, she first played in Goldoni’s The Villegiatura Trilogy and later in Chekhov's Three Sisters. Giorgio Barberio Corsetti cast her as Madame de Champigny in Labiche’s An Italian Straw Hat while Éric Ruf entrusted her with the role of Lady Capulet in Shakespeare’s Romeo and Juliet. She reunited with Christophe Lidon for Dürrenmatt’s La Visite de la vieille dame, and worked with Galin Stoev on Molière’s Tartuffe as well as with Lars Norén on his own play Poussière.

Her Portrait d'actrice has been reveal during the first Nuit du jeu broadcasted on decembre 20, 2022. The interveiw is available on YouTube.

For television, Danièle Lebrun has played in dramas by Alain Tasma, Robert Guédiguian, François Luciani, Philippe de Broca and Bernard Stora as well as in Marcel Bluwal’s theatre adaptations including: Le Jeu de l’amour et du hasard and La Double Inconstance both by Marivaux and Lulu by Frank Wedekind. She also played Baronness Roxane de Saint-Gély in Marcel Bluwal’s successful series Vidocq and Les Nouvelles Aventures de Vidocq. Along with playing in films by Claude Berri, Éric Rohmer and Sylvie Testud, Danièle Lebrun was directed on film by Bruno Nuyten in Camille Claudel, Jacques Audiard in A Self Made Hero (Un héros très discret) and Matthieu Kassovitz in Assassin(s).

During the 2018/2019 season, she can be seen in Hans Christian Andersen’s The Little Mermaid by Géraldine Martineau, Les Oubliés (Alger-Paris) written and directed by Julie Bertin and Jade Herbulot – Le Birgit Ensemble, and Hors la loi written and directed by Pauline Bureau.