It was founded in the aftermath of the 1925 Scopes trial to establish an institution of higher education that would teach from a Christian worldview.

During the Scopes trial in 1925, William Jennings Bryan expressed the wish that a school might be established in Dayton, Tennessee, "to teach truth from a Biblical perspective".

Its stated purpose was to provide "for the purpose of establishing, conducting, and perpetuating a university for the higher education of men and women under auspices distinctly Christian and spiritual, as a testimony to the supreme glory of the Lord Jesus Christ, and to the Divine inspiration and infallibility of the Bible,"[3] In 1958, it was designated William Jennings Bryan College, and the name was shortened to Bryan College in 1993.

[9] Its association with the Scopes trial has led to its addition as a stop along the Southeast Tennessee Religious Trail.

[18] On April 14th, 2023, Bryan College hosted an open house and a ribbon cutting ceremony to celebrate the official opening of the Clara Ward School of Nursing, allowing Bryan College students to pursue an undergraduate degree in nursing.

[26] In February 2014, college administrators supplemented the original statement of belief, which is included in the employment contract of professors, with the declaration that Adam and Eve "are historical persons created by God in a special formative act, and not from previously existing life forms."

[28] Two tenured faculty had their contracts terminated after refusing to agree to the revised statement of belief, and filed a lawsuit against the college in May 2014.

The following year, Livesay instituted procedural rules that faculty members claimed made it extremely difficult for them to hold meetings.

[31][32][33] They were also a member of the National Christian College Athletic Association, primarily competing as an independent in the Mid-East Region of the Division I level.

[37] In 2012, President Stephen Livesay prevented a student news story from being run, which revealed the coverup of the arrest of a faculty member.