Columbia College was formed in 1854 by a vote of the South Carolina Methodist Conference and was originally called Columbia Female College. Located in Columbia, South Carolina, the college was given the mission to "educate young women for fruitful service to church, state and nation." The College actually opened for classes in 1859 on what is now Hampton Street in downtown Columbia. The original class consisted of 121 women and 16 faculty members. The girls took courses in math, science, grammar and composition, Latin and religion/philosophy. For a fee the girls could also enroll in music, French or several types of art classes. Though the College continued to grow, in 1865 it was forced to shut its doors due to General Sherman's march on Columbia.

In 1873, the doors to Columbia Female College reopened and the College continued to grow. By 1882 an alumnae association had been established, making Columbia Female College the fifth female college in the nation to establish this type of organization.

Columbia Female College saw its first fire in 1895. Then in 1904 a tract of land was given to the school on North Main St. in North Columbia. This is the current location of the college. In 1905, the word "female" was droped from the name of the school. A second fire swept the school in 1909. This forced the college to operate out of its original facilities until 1910 when North Main could be reopened.

In 1938 the school gained accreditation from the Southern Association of Colleges and Schools. For a short period of time, Wofford and Columbia College was headed by the same president and board of trustees. By the 1950s that decision had been reversed and R. Wright Spears had taken the helm at Columbia College.

The campus, which had been steadily growing under Dr. Spears' command, was ravaged by yet another fire. In the midst of the tragedy, which destroyed a dormatory and classroom building, President Spears said "nothing has been destroyed that cannot be rebuilt." The only thing remaining from Old Main were the columns, which are now a symbol of the school. During the Civil Rights Movement the college, led by Dr. Spears, peacefully integrated and enrolled itsfirst African American student in 1966.

During the years between 1977 and 1997, the college had two presidents. Dr. Ralph Mirse served as president from 1977 to 1988 and was succeeded by Dr. Peter Mitchell. The school continued to grow under these two presidents.

In 1998, the first female president of Columbia College was inaugurated. Dr. Phyllis O. Bonanno worked to globalize the college. She made it her mission to prepare young women to find their place in the global economy. In 2000, Dr. James Rex took over the helm as a transitional president. In 2001 he was succeeded by Dr. Caroline Whitson. In 2006, Dr. Whitson unveiled her plan for Columbia College. The plan started with the 4-year curriculum of the 4Cs: Courage, Commitment, Confidence, Competence.