Originally established in 1963 as the Conservation Analytical Laboratory, principally to provide technical support for the collection conservation needs of Smithsonian museums the Laboratory began in 1983 to embark on a mission of independently formulated programs in research and education in conservation and scientific studies of collection materials, serving a nationwide and international professional audience. In January 1998 the Board of Regents of the Smithsonian Institution voted to rename the Conservation Analytical Laboratory (CAL) as the Smithsonian Center for Materials Research and Education to better reflect the present mission of SCMRE: research and education in the conservation, preservation, technical study and analysis of museum collection items and related materials.

The first Director of the unit was Charles H. Olin, 1966-1967. He was followed by Robert M. Organ, 1968-1983, and, after a vacancy in 1984, by Lambertus Van Zelst, 1985- .