Sources disagree as to Randolph’s birthplace (New York or Virginia). He was a free man of mixed-race ancestry, descendant of William Randolph. He described his mother as a beautiful sang melee of various strains of blood. SHe had some madagascan, French, Spanish, Indian and Oriental in her. His fathers blood he described as English, Celtic, Cymrizn, Teutonic and Morrish. He denied having African blood.

His father was a nephew of John Randolph of Roanoke and his background led to his being a spokesman for the abolition of slavery. He trained as a doctor of medicine and travelled widely in his youth where his interest in mysticism and the occult can be traced. Randolph worked on a sailing vessel, journeyed through Europe and as far east as Persia. A peripatetic man, he lived in many places, including New Orleans, New York, San Francisco, and Toledo, Ohio. During his early public career, Randolph appeared on stage as a trance medium and advertised his services in magazines associated with the Spiritualist Movement. Like many Spiritualists, he lectured in favor of Abolition and after Emancipation, taught literacy to freed slaves in New Orleans.

Randolph founded the Fraternitas Rosae Crucis, the oldest Rosicrucian organization in the United States, which today avoids mention of his interest in sex magic. These magico-sexual theories and techniques formed the basis of much of the teachings of The Hermetic Brotherhood of Luxor, although it is not clear whether or not Randolph himself was ever actually associated with the Brotherhood . Famous occultists and practitioners of sex magic Theodor Reuss and Aleister Crowley were heavily influenced by Randolph in both organizing the Ordo Templi Orientis (O.T.O.) and their sex magic rituals.

In 1851, Randolph made the acquaintance of Abraham Lincoln. Their friendship was close enough that, when Lincoln was assassinated in 1865, Randolph accompanied Lincoln’s funeral procession in a train to Springfield, Illinois. However, Randolph was asked to leave the train when some objected to the presence of such an African American descendent. He authored more than fifty books or pamphlets on magic and medicine, established an independent publishing company and was an avid promoter of birth control.