Lewis Payne may refer to:

• Lewis Powell (conspirator) (1844–1865), also known as Lewis Payne, American Confederate soldier who attempted to assassinate William H. Seward.
• Lewis F. Payne Jr. (born 1945), American politician from Virginia
• Lewis S. Payne (1819–1898), American merchant, Union Army officer, and politician from New York
• Lewis Payne (footballer) (born 2004), English association footballer