Andrei Aleksandrovich Orlov was born in 1960 in the Soviet Union and grew up in its capital, Moscow, where he attended high school № 736, graduating in 1977. After high school, as every male of age 18 in the Soviet Union, Orlov was drafted for two years of mandatory service in the Soviet Army. He finished his service in 1980 as a senior sergeant of anti-aircraft missile regiment.

In 1998, Orlov entered a Ph. D. program at Marquette University (Milwaukee, Wisconsin). The time which he spent at Marquette, first as a Ph.D. student and then as a faculty member, became the most stimulating and rewarding scholarly environment of his life, where his earlier ideas eventually crystalized into many books and articles. Here, under the guidance of Alexander Golitzin and other professors, he continued his study of Jewish and Christian apocalypticism and mysticism. In 2003, under the direction of Deirdre Dempsey and with Golitzin on his dissertation board, Orlov defended a Ph.D. dissertation on the development of Enochic lore. His dissertation covered early Mesopotamian traditions about the seventh antediluvian hero to the later Jewish Hekhalot testimonies in which Enoch became identified with the supreme angel Metatron. This study was hailed as a major contribution to the field of the Second Temple studies and later was published by Mohr-Siebeck. In 2004 Orlov was hired by his alma mater as a professor of Judaism and Christianity in Antiquity and he obtained a full professorship at Marquette University in 2012.