Wake Forest Institute was founded in the Baptist State Convention of 1833 in Rockingham, North Carolina. The North Carolina Baptist State Convention acquired a 616-acre land somewhere in the north of Raleigh from Calvin Jones. The region was called “Forest of Wake,” hence the name Wake Forest Institute. The institute opened its doors on February 3, 1834. The school initially aimed to educate Baptist ministers and laypeople and was called the Wake Forest Manual Labor Institute. Students, as well as the staff and faculty, were obliged to perform manual labor in the plantation for half a day. The pioneer principal was Samuel Wait, who later on became the president.

Five years after its establishment, the manual system was stopped, and the school changed its name to Wake Forest College. The settlement near the college was named Wake Forest. The school was forced to close during the American Civil War, in 1862 because of the students and faculty members served the Confederate States Army. In 1866, Wake Forest College reopened and grew in the next years. The School of Law was founded in 1894. In 1902, the School of Medicine was established. In 1921, the college had its historic first summer session. The Lea Laboratory was constructed between 1887 and 1888.

William L. Poteat was the main college figure in the early 20th century. He led the continuous growth of the college and was the first layman to assume the presidency in the college. He employed many excellent professors and worked on the expansion of the science curriculum. He expressed great support for the teaching of the theory of evolution, which caused arguments among the North Carolina Baptists. He, later on, got the formal support for academic freedom from the Baptist State Convention.

In 1941, under the leadership of Dean Coy Cornelius, the School of Medicine relocated to Winston-Salem. Cornelius also guided the college in its transition to a four-year college from a two-year program. The name of the school was changed to Bowman Gray School of Medicine. After a year, the first female undergraduate students were enrolled in Wake Forest College.

Smith Reynolds Foundation donated substantial gifts in 1946, which led to the relocation of the college to Winston-Salem. It had its full completion in the fall of 1956 under Harold W. Tribble’s supervision. Fourteen new buildings were established between 1952 and 1956, following the donation of Charles and Mary Reynolds of 35—acre of land. The buildings built had the Georgian design. The old school of Wake Forest was purchased by the Baptist State Convention and established the Southeastern Baptist Theological Seminary.

The college’s desegregation happened on April 27, 1962, after Edward Reynolds, a native of Ghana was admitted as an undergraduate student. In 1964, Reynolds became the first black graduate of the college.

In 1961, a graduate studies program was established. After six years, the full accreditation of Wake Forest University took place. In 1959, the School of Business, formerly Babcock Graduate School of Management, was founded. Wake Forest became autonomous in 1986 and established a fraternal relationship with the Baptist State Convention of Winston-Salem, North Carolina.