Various types of boards have governed the institution since its inception as Grand Junction Junior College in 1925. The first board of trustees was appointed on June 12, 1925 by Governor Clarence Morley for a term of two years. It included only three members: R. E. Tope, superintendent of schools and one of the key figures in the establishment of the junior college; C. E. Cherrington; and D. B. Wright.

The junior college had been established with the idea that it would be an extension of the University of Colorado in Boulder, and the small board may have reflected this. This style of board continued until legislation allowing the establishment of junior college districts resulted in the county voting to form the Mesa County Junior College District and Mesa College in 1937. The junior college district board consisted of five people elected by a delegation of school board directors. The first board included J. A. Edling of Appleton, Carl Potter of Collbran, M. L. Dilley of Clifton, Josephine Biggs of Grand Junction, and R. H. Penberthy of Grand Junction.

The junior college district continued until the college expanded beyond its ability to raise mill levies any further. A need for money and a community desire for a four-year college resulted in efforts to transition the college from a local junior college to a state college. On April 19, 1972, Governor John Love signed the bill to make Mesa College into a baccalaureate-granting institution with a goal of accreditation in fall 1974. On January 15, 1974, the voters of Mesa County voted for the dissolution of the Mesa Junior College District, and Mesa College became a state baccalaureate institution under the control of the Trustees of the State Colleges in Colorado. With three other institutions under the Trustees of the State Colleges in Colorado, Mesa College went from controlling its own development and instructional offerings to competing with other institutions and with final decisions being made by the state board. The college experienced limited growth during its time under the Trustees of the State Colleges in Colorado, except for the development of the Bishop Campus for the Unified Technical Education Center (formerly, Western Colorado Community College and now CMU Tech) and the establishment of the Montrose Campus. In 1988 the state board mandated a name change for Mesa College, and it became Mesa State College to align with the names of the other four-year colleges under the state board. MSC continued under the state board until the needs of the four colleges began to surpass the board’s ability to facilitate. In June 2003, the state board was dissolved and each of the four colleges formerly under its control were granted their own independent boards of trustees. This paved the way for each college to determine its own trajectory and focus within its mandate from the state. Governor Bill Owens appointed the members of the first Mesa State College Board of Trustees: Luis Colón, Lena Elliott, Jamie Hamilton, Thomas Kaesemeyer, Steve Meyer, Charlie Monfort, Carol Nesland, James Wexels, and Jane North. This transition coincided with the resignation of President Michael Gallagher in 2002 and an interim served until the Mesa State College Board of Trustees hired President Tim Foster in 2004, starting a period of expansion and success for the college and the eventual transition to university status. On August 10, 2011, Mesa State College became a university under the name Colorado Mesa University. The Board of Trustees of Colorado Mesa University continues to lead the institution.