Israel Regardie was born Israel Regudy in London to Barnet Regudy, a cigarette maker, and his wife, Phoebe Perry, poor orthodox Jewish immigrants from Zhitomir, Russia. His family changed their surname to "Regardie" after a clerical mixup resulted in Israel's brother being enrolled in the British Army under that name. Regardie emigrated with his parents to the United States in August 1921 and settled in Washington, DC. He studied art in Washington, DC and Philadelphia, PA. With a Hebrew tutor he gained a linguistic knowledge which would prove invaluable in his later studies of Hermetic Qabalah. With easy access to the Library of Congress, he read widely and became interested in theosophy, Hindu philosophy and yoga. He also joined the Rosicrucians at around this time.

After reading Part I of Magick by the occultist Aleister Crowley, Regardie initiated a correspondence which led to his return at 21 to the U.K. at Crowley's 1928 invitation to become his secretary. When the two parted company four years later, in 1932, Regardie distanced himself from Crowley personally, but still retained a great deal of respect for his writings. Shortly after this period he published The Tree of Life, a guide to magick, largely derived from Crowley's work, and A Garden of Pomegranates, a primer on Qabalah based on notes he had taken while working for Crowley. Regardie would later write a biography of Crowley, The Eye in the Triangle, and continue to edit and republish Crowley's works up until the 1970s.

In 1934 Regardie joined Stella Matutina, a successor organization of the Hermetic Order of the Golden Dawn. When the group disbanded, Regardie acquired the bulk of the Order's documents and compiled the book, The Golden Dawn, which earned him the enmity of many of the other former members and the reputation of being an oath-breaker because of the information it revealed. However, the book transformed the work of the Order into an entirely new branch of the Western Occult Tradition. As Regardie observed in his work A Garden of Pomegranates, "...it is essential that the whole system should be publicly exhibited so that it may not be lost to mankind. For it is the heritage of every man and woman — their spiritual birthright." The various occult organizations claiming descent from the original Golden Dawn, and the systems of magic practiced by them, owe their continuing existence and popularity to Regardie's work.

In 1937, at the age of 30, Regardie returned to the U.S., entering Chiropractic College in New York City. In addition, he studied psychoanalysis with Dr. E. Clegg and Dr. J. L. Bendit, and psychotherapy with Dr. Nandor Fodor. He opened a chiropractic office and taught psychiatry — Reichian, Freudian, and Jungian — retiring in 1981 at the age of 74, when he moved to Sedona, Arizona.

Regardie died from a heart attack in the presence of close friends during a dinner at a restaurant in Sedona, Arizona on March 10, 1985 at the age of 77.

Regardie is a principal reliable source for much of what is known about the Hermetic Order of the Golden Dawn. His writings and the students he taught or influenced provide much of the foundation for modern Western occultism. In addition to preserving the knowledge, Regardie also preserved a valid branch of the initiatory lineage of the Golden Dawn in America:

The second significant task carried out by Regardie was, as an Adept, to bring a valid branch of the initiatory lineage of the Golden Dawn to America the alchemical melting pot where the New Age was incubating. Such tasks are not always easy. A. M. A. G. waited here four decades until the threads of the pattern came together. Then, in one of those graceful synchronicities which often play midwife to significant magical events, a couple in Georgia were inspired...at that time scarcely aware of what they were undertaking ... to build a Rosicrucian Vault, the powerful ritual chamber required to pass on the Adept Initiation, at precisely the time when two magicians (one on the east coast of the United States and one on the west coast), unknown to each other or to the Georgia couple, came to be ready to receive that Initiation. And A.M.A.G., with the right to confer the Initiation in such a Vault, was the connecting link among them. And so, in one remarkable weekend, Regardie presided over two Initiations into the Inner Order, the first and the last which he ever performed; and the Lamp of the Keryx was passed into American hands. — Forrest, Adam P. in Cicero (1995), p. 541

Note: In the above paragraph, A.M.A.G. refers to Regardie. Participants in the Order took on a pseudonym or magical motto. In Regardie's case, his pseudonym was Ad Majorem Adonai Gloriam which means "To the Greater Glory of Adonai".