Following the hiatus in University operations caused by the Civil War, the University of Tennessee's trustees named Thomas William Humes (1815-1892) president in July 1865. It was not until a year later, however, that the institution could resume operations. Humes was a Knoxville native and had graduated from East Tennessee College in 1830 at the age of 15. During Humes's administration, great strides were taken to reorganize and rehabilitate the war-torn campus, including the erection of several new buildings, the addition of new faculty, the addition of medical and dental departments (then located in Nashville), the establishment of an agricultural experiment station, and the state Legislature's 1879 redesignation of the institution as the University of Tennessee. Enrollment also increased, reaching a high of 315 in 1874. In spite of these advances, much of Humes's time in office was occupied by bitter contention between those who would shift the University's curricular emphasis to the agricultural and mechanical arts and those who would retain the traditional academic framework of classics and humanities. Humes stood with the traditionalists, and this stance led to his downfall. The trustees asked for his resignation, and on August 24, 1883, Humes complied.

Humes was not replaced immediately, and the Chairman of the Faculty led the University from 1883 to 1887. The Trustees finally appointed Charles William Dabney (1855-1945) President in 1887. He was the first President to hold a PhD and did much to make the century-old institution on the Hill a university in fact as well as in name. He built a research institution with new laboratories, dormitories, a gymnasium, a library, and further developed the College of Agriculture. He re-organized the faculty and in 1893 women were officially admitted to the University. The Summer School of the South was also implemented during his tenure.