James Wayne may refer to:
- James Moore Wayne (1790–1867), U.S. Supreme Court Justice and U.S. Representative
- SS James M. Wayne, a Liberty ship
- James Wayne (R&B musician) (1920–1978), American rhythm and blues musician who also recorded as James Waynes and "Wild Willie" Wayne
- Jimmy Wayne (born 1972), American country musician
- Jim Wayne, member of the Kentucky House of Representatives
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