Lebeau married actor Marcel Dalio in 1939; it was his second marriage. They had met while performing a play together. She had already appeared in her first film, an uncredited role as a student in the melodrama Young Girls in Trouble (Jeunes filles en détresse, 1939). In June 1940, Lebeau and Dalio (who was Jewish) fled Paris ahead of the invading German Army and reached Lisbon. They are presumed to have received transit visas from Aristides de Sousa Mendes, allowing them to enter Spain and journey on to Portugal. It took them two months to obtain visas to Chile.

However, when their ship, the S.S. Quanza, stopped in Mexico, they were stranded, along with around 200 other passengers, when the Chilean visas they had purchased turned out to be forgeries. Eventually, they were able to get temporary Canadian passports and entered the United States. Lebeau made her Hollywood debut in Hold Back the Dawn (1941), which featured Charles Boyer and Olivia de Havilland in the leading roles. The following year, she appeared in the Errol Flynn movie Gentleman Jim, a biography of Irish-American boxer James J. Corbett.

Later that year she was cast in the role of Yvonne, Humphrey Bogart's character's discarded mistress, in Casablanca. Warner Bros. signed her to a $100-a-week contract for twenty-six weeks to be in a number of films. On 22 June, while she was filming her scenes in Casablanca, her husband, Marcel Dalio, who played Emil the croupier in the same film, filed for divorce in Los Angeles on the grounds of desertion. They divorced in 1942. Shortly before the release of the film, Warner Bros. terminated her contract. After Joy Page died in April 2008, Lebeau was the last surviving credited cast member of Casablanca.

Following Casablanca, Lebeau appeared in two further American films. The first was a large role in the war drama Paris After Dark (1943), with her former husband. The following year, Lebeau had a smaller role in Music for Millions. She appeared on Broadway in the play The French Touch in a production directed by René Clair. After the end of World War II, Lebeau returned to France and continued her acting career. She appeared in Les Chouans (The Royalists, 1947) and worked in Great Britain, appearing in a film with Jean Simmons, Cage of Gold (1950).

She would appear in 20 more films, mainly French, including La Parisienne (1957), with Brigitte Bardot as the star, and Federico Fellini's 8½ (1963). Lebeau's last two films were Spanish productions in 1965.

In 1988, she married, thirdly, to Italian Screenwriter Tullio Pinelli who had contributed to the script of 8½.

She told Charlotte Chandler, author of a biography of female lead Ingrid Bergman, in the 1990s: "It wasn't that I was cut out, it was because they kept changing the script, and each time they changed it, I had less of a part". "It was not personal, but I was so disappointed".

Lebeau died on 1 May 2016 in Estepona, Spain, aged 92, after breaking her thigh bone. French culture minister Audrey Azoulay said of Madelaine Lebeau after her death: "She was a free woman who lived by her own rules, totally inhabiting the roles entrusted to her by leading Director. She will forever be the face of French resistance."