The film is based on the actual events surrounding the Cuban missile crisis of 1962, taking place during the titular thirteen days wherein the U.S. and the Soviet Union nearly engaged in full-scale nuclear war. After President John F. Kennedy is shown photographs from a spy plane detailing the presence of missiles in Cuba capable of obliterating massive areas of the U.S., he must immediately decide the most effective course of action for the country. With the aid of best friend and special assistant Kenny O'Donnell and brother Robert, the President must avoid a dire chain of events that could be dictated by General Curtis LeMay, who would rather take immediate action and invade Cuba. After initial reticence about leaking the information to the nation, President Kennedy eventually tells of the conflict, leading to widespread panic and a blockade of Cuba. With the aid of Robert McNamara and Adlai Stevenson, the leaders must find a way to alleviate the tension of the situation.