The school, located on Commerce Street in the downtown Starr Hill neighborhood, was built in four sections starting in 1926, with additions made in 1938–39, 1958, and 1959.

[9] In 1943, there were fourteen teachers, of whom five were male, led by principal Owen J. Duncan, Jr., and 54 graduating seniors, 55 juniors, 56 sophomores, and 63 freshmen.

[13] The school newspaper was called The Jeffersonian and included editorial staff, sportswriters, features writers, and advertising and circulation managers by 1941.

In 1941 the Jefferson High School Music Department consisted of a school band and three organized groups: the girls' glee club; the Singing Privateers, an all-male chorus; and a mixed chorus of sixty voices, representing a combination of the two former groups.

The Jefferson High School yearbook was named the Crimson and Black, and had a staff of eighteen by the 1944–1945 academic year.

[17] The 1944 yearbook was dedicated to "...The boys of the Jefferson High School who have willingly answered the call of our country and who are serving in the armed forces to bring to our land once more a lasting peace."

[19] In 2005, the building was proposed to be added to the National Register of Historic Places, and it received that designation in 2006.