Botany was first taught at Ohio Wesleyan in 1845 by Professor (later President) Frederick Merrick. This early single course emphasized collecting and classifying plants. In the latter part of the nineteenth century after a period of time in which the botany course was a part of a Natural History department, Dr. Albert Mann, a botanist, began teaching the subject. During his tenure a greenhouse was established, laboratory equipment was added, and course work expanded to two full years.

Shortly after his arrival on campus in 1913, Dr. Claude E. O'Neal became the first chairman of the newly-organized Department of Botany. He held this post until his retirement in 1954. During the O'Neal era course offerings and equipment were greatly expanded and modernized. The size of the staff was rapidly increased, particularly following World War II. The first bacteriology course was added during World War II, and this subject achieved growing importance in the ensuing years as recognized in the change in the departmental name to Botany and Bacteriology. In 1962 the Department moved from Merrick Hall (completed in 1873) to modern and expanded facilities in Bigelow-Rice Hall with its attached Claude E. O'Neal Greenhouse. In the new building laboratory facilities for bacteriology, cytology, and physiology were particularly complete and up-to-date, as were the rooms for the introductory courses. Additionally, the department shared use of a transmission electron microscope with the nearby U.S.D.A. laboratories. In the late 1990's a scanning electron microscope with cryo and EDS was purchased and housed in the George W. Burns Microscopy Laboratories.

A new chapter in the department's history has unfolded with the move into the University's new Conrades-Wetherell Science Center. A new greenhouse, an integral part of the new Center, was completed in May, 2002. This facility provides a new home for the department's plant collection and space for student and faculty research.