Born in Saint Petersburg, Russia, on September 4, 1900, Hoyningen-Huene was the only son of Baron Barthold Theodorevitch von Hoyningen-Huene (1859-1942), a Baltic nobleman and military officer, and his wife, Emily Anne "Nan" Lothrop (1860-1927), a daughter of George Van Ness Lothrop, an American minister to Russia. (The couple was married in Detroit, Michigan, in 1888.) He had two sisters. Helen (died 1976) became a fashion designer in France and the United States, using the name Helen de Huene. Elizabeth (1891-1973), also known as Betty, also became a fashion designer (using the name Mme. Yteb in the 1920s and 1930s) and married, first, Baron Wrangel, and, second, Lt. Col. Charles Norman Buzzard, a British Army officer.
During the Russian Revolution, the Hoyningen-Huenes fled to first London, and later Paris. By 1925 George had already worked his way up to chief of photography of the French Vogue. In 1931 he met Horst, the future photographer, who became his lover and frequent model, and traveled to England with him that winter. While there, they visited photographer Cecil Beaton, who was working for the British edition of Vogue. In 1931, Horst began his association with Vogue, publishing his first photograph in the French edition of Vogue in November of that year.
 United States
In 1935 Hoyningen-Huene moved to New York City where he did most of his work for Harper's Bazaar. He published two art books on Greece and Egypt before relocating to Hollywood, where he earned his wedge by shooting glamorous portraits for the film industry.
Hoyningen-Huene worked before anything resembling contemporay flash photography was known. Working in huge studios and with whatever lighting worked best. There is something about the texture of his black and whites that one seldom finds in contemporary work. Beyond fashion, he was a master portraitist as well from Hollywood stars to other celebrities.
He also worked in Hollywood in various capacities in the film industry, working closely with George Cukor, notably as special visual and color consultant for the 1954 Judy Garland movie A Star Is Born. He served a similar role for the 1957 film Les Girls, which starred Kay Kendall and Mitzi Gaynor and the Sophia Loren film Heller in Pink Tights.
He died at 68 years of age in Los Angeles.
Hoyningen-Huene is a relative of the 1970s porn star Peter Berlin.