Chipola College was founded in 1947 and operated for one year as a private educational institution.

Florida's Minimum Foundation Law, passed in 1947, included provisions for public support of colleges. Under the provisions of this law, a college district consisting of Jackson, Calhoun, and Washington Counties was approved to operate as a public institution with financial support from the three counties and the State of Florida. This approval was granted by the State Board of Education, and Chipola Junior College became a public institution effective September 1, 1948.

The original district of Calhoun, Jackson and Washington Counties was expanded later to include Holmes and Liberty Counties.

A milestone in the history of Chipola occurred in 1953 when the campus moved from its original location at the former Marianna Army Air Base to the present location. The first permanent buildings were completed and occupied in 1954. Additions through the years have brought the number of buildings to seventeen. The campus also includes outdoor physical education fields and a pool. Programs in vocational education were begun in 1967-68.

Evidence of growth with regard to official recognition by other institutions of higher learning came in 1957 when the college was accepted into membership and fully accredited by the Southern Association of Colleges and Schools. This accreditation was reaffirmed in 1968, 1978, 1988, 1998, 2008, and 2018.

Originally known as Chipola Junior College, the institution entered in a new stage when it officially became Chipola College on August 18, 2003.  The name was changed to reflect the college's new mission of offering 4 year degrees in Education, Business and Nursing.