It resulted from the 1968 merger of historically black colleges and other schools established by northern Protestant missions during and after the American Civil War.

This was one of more than ten schools founded by the AMA, an integrated organization led by black and white Congregational, Methodist and Presbyterian ministers.

The school was established soon after the occupation of Memphis by Federal troops during the Civil War; they were based at Camp Shiloh outside the city limits to the south.

In 1870, Francis Julius LeMoyne (1798–1879), a Washington, Pennsylvania doctor, donated $20,000 (~$425,287 in 2023) to the American Missionary Association to build an elementary and secondary school for prospective teachers.

Under the leadership of the third principal, Andrew J. Steele, the school enjoyed three decades of growth and development.

[5] In August 2007, the City of Memphis ensured the college would open for the fall 2007 semester by pledging $3 million in taxpayer funds to be added to other substantial pledges from the United Negro College Fund, Cummins, radio host Tom Joyner and the United Church of Christ.

A $40 million pledge from the Community Foundation of Greater Memphis quadrupled the college's endowment.

It is roughly bounded by Walker, Hollis Price, Crown and alley to rear of Sweeney Hall.

[8] It includes Steel Hall, built in 1914, the oldest and original building on this campus, which was designed by Tandy & Foster and is separately listed on the National Register.

[9] It includes two Colonial Revival buildings, Brownlee and Sweeney halls, which were designed by George Awsumb along with the quadrangle in 1936.