Harry Horner was born in Bohemia (now Czech Republic), but spent most of his early life in Austria. In 1934, he graduated from the University of Vienna with a degree in architecture. Along the way, he also managed to study dramatic arts, directing and costume design, making his stage debut as an actor with the Max Reinhardt Theatre Company. He joined the troupe during their 1936 tour of the United States as assistant to Reinhardt.Putting every facet of his training to use, he worked variously as actor ("Iron Men", 1936), associate musical director and conductor ("The Eternal Road", 1937); and, finally, scenic designer ("All the Living", 1938).

In 1940, Horner became a naturalised American citizen and went to Hollywood, having formed an association with the noted production designer William Cameron Menzies. He assisted Menzies on the generational drama Our Town (1940), then joined the U.S. Army Air Force on specialised duties to work on morale-building projects, such as Stage Door Canteen (1943) (as production designer). Under air force supervision, he then created the sets for Winged Victory (1944), based on a Moss Hart play about pilot recruitment and training. Following the war, Horner divided his time between the stage and Hollywood. He won the first of two Academy Awards for Miras (1949) (in collaboration with John Meehan), having done meticulous and painstaking research on period detail, collecting numerous contemporary photographs. Three years later, he branched out into directing with the cult sci-fi Red Planet Mars (1952), followed by the stylish film noir Beware, My Lovely (1952) (eliciting power-house performances from his stars Robert Ryan and Ida Lupino).

Throughout the remainder of the decade, Horner remained active as a designer on Broadway, including the play "Tovarich" (which he also staged). He also turned his attention to designing and directing for both the Metropolitan and the San Francisco Opera, as well as finding time to direct a number of early television episodes. For the big screen, he worked as production designer on diverse projects, always at his best on famous literary adaptations, such as Dünkü çocuk (1950) and Ayrı masalar (1958), and winning his second Academy Award for the gritty Robert Rossen drama, Bilardocu (1961). As with all his assignments, he conducted extensive research on the milieu by visiting countless pool halls in order to imbue both picture and characters with the necessary complexity and realism. Horner was nominated for a third Oscar for Son gerçek (1969). He was inducted into the Art Director's Guild Hall of Fame in 2006.