Advertising executive Roger Thornhill (Cary Grant) finds himself in a case of mistaken identity, as members of a strange organisation believe he is a man by the name of George Kaplan due to a miscommunication. With no other option, he flees across the country, being pursued by enemies of the government who are convinced that he is a secret agent.

He finds a friend in Eve Kendall (Eve Marie Saint) who helps to conceal him during a perilous train journey, but he soon discovers that she is not all she seems.