Prewitt studied geology at Massachusetts Institute of Technology as an undergraduate and received his PhD in 1962 in crystallography at the same place under the supervision of Martin Buerger, where he worked on the structure determination of wollastonites and pectolites. He moved to DuPont Central Research Laboratory in Wilmington, Delaware, where he worked with Robert D. Shannon to compile the effective ionic radii, which became an important foundation of modern crystal chemistry. Afterwards, Prewitt became a professor at Stony Brook University in 1969. In 1986, he was hired by the Carnegie Institute of Science to head the Geophysics Laboratory until 1998. He later became an adjunt faculty member at University of Arizona.