Professional photographer L.B. "Jeff" Jeffries breaks his leg while getting an action shot at an auto race. Confined to his New York apartment, he spends his time looking out of the rear window observing the neighbors. He begins to suspect that a man across the courtyard may have murdered his wife. Jeff enlists the help of his high society fashion-consultant girlfriend Lisa Freemont and his visiting nurse Stella to investigate.
Madison Avenue advertising man Roger Thornhill finds himself thrust into the world of spies when he is mistaken for a man by the name of George Kaplan. Foreign spy Philip Vandamm and his henchman Leonard try to eliminate him but when Thornhill tries to make sense of the case, he is framed for murder. Now on the run from the police, he manages to board the 20th Century Limited bound for Chicago where he meets a beautiful blond, Eve Kendall, who helps him to evade the authorities. His world is turned upside down yet again when he learns that Eve isn't the innocent bystander he thought she was. Not all is as it seems however, leading to a dramatic rescue and escape at the top of Mt. Rushmore.