As a result of efforts undertaken together by the Synod of Virginia and the Synod of North Carolina, Union Theological Seminary was founded in 1812 as the theological department of Hampden–Sydney College, located near Farmville, Virginia, and housed in what is now named Venable Hall.

The Charlotte campus for Union Presbyterian was relocated to its new facility on 5141 Sharon Road in 2012.

For many years, the seminary operated WRFK, an FM radio station at 106.5 MHz.

Faculty come from a range of denominational backgrounds, including Baptist, Lutheran, and Methodist.

Notable retired faculty include Bible scholar James L. Mays and Brian Blount.