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Brooks began his career as a comic and a writer for Sid Caesar's variety show Your Show of Shows(1950–1954). There, he worked with Neil Simon, Woody Allen, Larry Gelbart, and Carl Reiner. With Reiner, he co-created the comedy sketch The 2000 Year Old Man. He released several comedy albums, starting with 2000 Year Old Man in 1960. Brooks received five nominations for the Grammy Award for Best Comedy Album, finally winning in 1999. With Buck Henry, he created the hit satirical spy comedy series Get Smart (1965–1970) on NBC television.

Brooks won the Academy Award for Best Original Screenplay for The Producers (1967). He then rose to prominence by directing a string of successful comedy films such as The Twelve Chairs (1970), Blazing Saddles (1974), Young Frankenstein (1974), Silent Movie (1976), and High Anxiety (1977). Later, Brooks made History of the World, Part I (1981), Spaceballs (1987), Life Stinks (1991), Robin Hood: Men in Tights (1993), and Dracula: Dead and Loving It (1995). A musical adaptation of his first film, The Producers, ran on Broadway from 2001 to 2007 and earned Brooks three Tony Awards. The project was remade into a musical film in 2005. He wrote and produced the Hulu series History of the World, Part II (2023).

Brooks was married to actress Anne Bancroft from 1964 until she died in 2005. Their son, Max Brooks, is an actor and author known for his novel World War Z: An Oral History of the Zombie War (2006). In 2021, Mel Brooks published his memoir titled All About Me!. Three of his films are included on the American Film Institute's list of the top 100 comedy films of the past 100 years (1900–2000), all of which were ranked in the top 15: Blazing Saddles at number 6, The Producers at number 11, and Young Frankenstein at number 13.