The Biophysics Department was established with funds from Mrs. May McShane Jenkins and named in honor of her late husband Thomas Courtenay Jenkins (1866-1938), a Baltimore financier and art collector. Mrs. Jenkins was always interested in physiotherapy. Her eagerness (as her will stated) to encourage exploration of "water, heat, and light in the treatment of disease" led Mrs. Jenkins to make donations in 1947 and 1955 for the study of biophysics at Johns Hopkins. Upon her death in 1957 the University received the bulk of her estate to endow the Thomas C. Jenkins Department of Biophysics. A final distribution took place in 2000.

In 1949, the first course in biophysics was offered at Johns Hopkins. The following year Jenkins Hall was dedicated as the center of biophysical research at the Homewood campus. In 1953, the first Chairman of Biophysics Dr. F. Keffer Hartline (1967 Nobel Prize winner in Physiology or Medicine) left the University and was replaced the following year by Dr. Francis "Spike" Carlson, who was part of the faculty group to start biophysics here. He served until 1971 and under his leadership in 1956 "fundamental studies" in biophysics was formally established as the separate Thomas C. Jenkins Department of Biophysics in the Faculty of Philosophy (the predecessor of the School of Arts and Sciences). Medicine and health studies in biophysics were placed under the Schools of Medicine and Public Health, respectively. Jenkins Hall was expanded to its current size three years later.

In accepting Mrs. Jenkins' 1957 bequest, Dr. Milton S. Eisenhower, then President of Johns Hopkins explained the significance of biophysics. "The interrelation of biology and physics is an important field of study. There are few investigators with the thorough training of both biology and physics who can do advanced work in the combined biophysics field. Johns Hopkins is performing a unique service in producing investigators who are capable of advancing biology in terms of physics and mathematics."

Faculty from other disciplines who are oriented towards biophysics receive joint appointments. The department was involved in the Program in Molecular and Computational Biophysics (PMCB) and the Institute for Multiscale Modeling of Biological Interactions (IMMBI). In the mid 1980s, Jenkins Hall was completely renovated, allowing the department to easily take advantage of the burgeoning use of computers and other new technologies. This permitted the installation of a University-run computer lab. The building has been upgraded several times; an x-ray crystallography lab was added in 2000.