The film opens with the MGM logo, as usual, but with a voice-over saying, “I forgot the opening line” (the voice of James Stewart), replacing the lion roar, and proceeds with The Lecturer regaling his unseen students with a wealth of knowledge of the habits of birds. Owlish Brewster McCloud, living hidden and alone under the Houston Astrodome, dreams of creating wings that will help him fly like a bird. His only assistance comes from Louise, a beautiful woman who wants to help. Wearing only a trench coat, Louise has unexplained scars on her shoulder blades, suggestive of a fallen angel. She warns him against having sexual intercourse, as this could kill his instinct to fly.
While Brewster works to complete his wings and condition himself for flight, Houston suffers a string of unexplained murders, the work of a serial killer whose victims are found strangled and covered in bird droppings. Haskell Weeks, a prominent figure in Houston, pulls strings to have the Houston Police call “San Francisco super cop” Frank Shaft to investigate. Shaft immediately fixates on the bird droppings and soon finds a link to Brewster. Brewster eludes the police with the apparent help of Louise but he eventually drives her away—and dooms himself—when he ignores her advice about sex by hooking up with Astrodome usher Suzanne Davis. Suzanne saves Brewster by evading Shaft in her AMC Gremlin (specially equipped for the film with a 401 cu.in. V8). Severely injured after losing Brewster, Frank kills himself. Brewster eventually confesses his responsibility in the killings to Suzanne, who betrays him to the police.
A small army of Houston policemen enter the Astrodome, but fail to nab Brewster before he takes flight using his completed wings. Although Brewster escapes the police, he cannot escape a human being’s inherent unsuitability for flight. Exhausted by the effort, he falls out of the air, crashing in a heap on the floor of the Astrodome. The film ends with a Circus entering the Astrodome, played by the cast of the film, costumed as clowns, strongmen and other circus performers. The Ringmaster (played by William Windom) announces the names of each cast member, finishing with Brewster, who remains crumpled on the floor.