William Gaines (1922–1992) was an American publisher, notably of Mad magazine.
William Gaines may also refer to:
Sportsmen Bill Gaines (basketball) (born 1946), American guard for San Diego Rockets Bill Gaines (sprinter), American 60 yard winner at 1968 USA Indoor Track and Field Championships William Gaines (American football) (born 1971), NFL defensive tackle
Others 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