In 1976, Smalley joined Rice University.  In 1982, he was appointed to the Gene and Norman Hackerman Chair in Chemistry at Rice. He helped to found the Rice Quantum Institute in 1979, serving as chairman from 1986 to 1996. In 1990, he became also a professor in the department of physics.  In 1990, he helped to found the Center for Nanoscale Science and Technology.  In 1996, he was appointed its director.
He became a member of the National Academy of Sciences in 1990, and the American Academy of Arts and Sciences in 1991.