1861
William Allen Tyree replaced Penick and served as the first principal during the war years. Tyree was a brother-in-law of Penick. Tyree served as principal until 1863.

1864
Having the word "union" in the college name during the war years proved an embarrassment to the community. The college's name was changed to Roanoke Female College (or, R.F.C.) after the largest of the three Baptist associations.

1867
Thomas Hume, Jr., joined R.F.C. as co-principal from 1867 to 1872. Under the leadership of Isaac Beverely Lake and Hume, the school enrolled 91 students for 1868.

1870
R.F.C. hired a third co-principal, Arnaud Eduard Preot who had come to Danville one year earlier to teach at the Methodist college.