He appeared in many prominent movies, including Casablanca (1942), in which he played Carl, the head waiter; Christmas in Connecticut (1945); In the Good Old Summertime (1949); and Lullaby of Broadway (1951).

His rotund body type and overall cuteness, coupled with his caring personal character, caused studio magnate Jack L. Warner to bestow on Sakall the affectionate nickname "Cuddles".

Besides his unique moniker, by which he was "known throughout the movie business", Sakall also earned a reputation as one of the "stalwart character-acting veterans" of his day, particularly given his "choice", "significant role" in Casablanca.

Author and media analyst Harlan Lebo of the University of Southern California later noted Sakall's "bubbly" and "colorful" nature on screen in the book Casablanca: Behind the Scenes.

He appeared in Familientag im Hause Prellstein (1927), Ihre Majestät die Liebe (1929, which was remade in Hollywood as Her Majesty, Love, with W.C. Fields in Sakall's role) and Two Hearts in Waltz Time (1930).

Sakall began a Hollywood career that included "an endless succession of excitable theatrical impresarios, lovable European uncles and befuddled shopkeepers".

Next, he played Otto Oberkugen in In the Good Old Summertime, with Judy Garland and Van Johnson – this was a musical remake of Ernst Lubitsch's The Shop Around the Corner (1940).

His other roles included Poppa Schultz in the Errol Flynn western Montana (1950); Miklos Teretzky in the June Haver musical The Daughter of Rosie O'Grady (also 1950); Don Miguel in the Randolph Scott western Sugarfoot; Uncle Felix in the musical Painting the Clouds with Sunshine (1951) with Virginia Mayo, and one of the episodes in the movie It's a Big Country (also 1951) featuring Gene Kelly, Van Johnson, Gary Cooper, Janet Leigh, Fredric March and Ethel Barrymore.