As early as 1980, a proposal was made to establish a regional Cultural Heritage Center at the University of Missouri-Columbia. Such a Center would serve primarily to focus the existing interests of the university community in cultural heritage, provide and seek funding sources for multidisciplinary cultural heritage research projects, and serve generally as an "information clearinghouse" for Missouri's cultural heritage.

The Missouri Cultural Heritage Center was established at the Columbia Campus in the fall of 1981 with startup funds drawn from the University's Weldon Spring Fund, and the Center officially opened in 1982. Initially run by a steering committee, the Center hired Howard Wight Marshall during the summer of 1982 to be its director, a position he held until the closing of the Center on June 30, 1993.

Much of the Center's work was funded through large grant support from the National Endowment for the Arts and the Missouri Arts Council. Among the significant contributions of the Center resulting from these grants was the development of the Traditional Arts Apprenticeship Program and Missouri Performing Traditions, both of which continued after the Center's closing as the Missouri Folk Arts Program. A further legacy of the Center is the Graduate Interdisciplinary Minor in Historic Preservation offered at the University of Missouri-Columbia.

Originally located at 400 Hitt Street in Columbia, the Center moved into the renovated Conley House at 602 Sanford Street in June, 1986. The name of the Center was changed to Cultural Heritage Center in June, 1989.

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