Her early career was dominated by the music hall, and she later appeared in plays and cabaret. Arletty was a stage performer for ten years before her film debut in 1930. Arletty’s career took off around 1936 when she appeared as the leading lady in the stage plays Les Joies du Capitole and Fric-Frac, in which she starred opposite Michel Simon. She later starred as Blanche in the French version of A Streetcar Named Desire.

Arletty was imprisoned in 1945 for her wartime liaison with a German Luftwaffe officer, Hans-Jürgen Soehring, during the occupation of France. She allegedly later commented on the experience, "My heart is French but my ass is international." Although other French women fell in love with German Soldiers, her romantic affiliation with Soehring during the German occupation prompted a charge of treason. James Lord wrote of her special treatment:

In 1995 the government of France issued a series of limited edition coins to commemorate the centenary of film that included a 100 Franc coin bearing the image of Arletty.

Marcel Carné was known for his poetic realism filmmaking style. Arletty’s minor role of Raymonde in his film, Hotel du Nord, garnered attention for her “Atmosphere! Atmosphere!” performance. In 1945 Arletty appeared in her most famous film role, the central part of Garance in Les Enfants du Paradis, her fourth role for the Director. For this role she earned one of the highest salaries ever in French cinema.