Samuel Klein may refer to:
- Samuel Klein (businessman) (born 1923), founder of the Casas Bahia chain of stores in Brazil
- Samuel Klein (doctor), doctor and nutritional expert based at Washington University
- Samuel Klein (scholar) (1886–1940), historian and geography researcher of the Land of Israel
- Sam Klein, lead character in the Allan Levine series by the same name
- Samuel Jacob Klein, (born 1978) professor, physicist, programmer, speaker, technologist and knowledge curator.