William Gaines (1922–1992) was an American publisher, notably ofMad magazine.

William Gaines may also refer to:

• Bill Gaines (basketball) (born 1946), American guard for San Diego Rockets
• Bill Gaines (sprinter), American 60 yard winner at1968 USA Indoor Track and Field Championships
• William Gaines (American football) (born 1971), NFL defensive tackle

• William Gaines (minister and community leader) (1824–1865), American freed slave during Reconstruction Era in Georgia
• William E. Gaines (1844–1912), American congressman from Virginia
• William Gaines (professor) (1933–2016), American Pulitzer Prize-winning investigative reporter

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