The film opens with Detective Chan rushing to the hospital to be with his daughter as she prepares to give birth to his first grandchild. While Charlie Chan waits at the hospital, his "number two" son Jimmy intercepts a message intended for Charlie about a murder on board the freighter ''Susan B. Jennings.''
Mary Whitman has arrived in Reno to obtain a divorce. While there, she is arrested on suspicion of murdering a fellow guest at her hotel (which specializes in divorcers).
Charlie and Jimmy Chan are traveling by plane to San Francisco. Jimmy befriends insurance executive Thomas Gregory. Charlie's friend, novelist Paul Essex, dies aboard the aircraft after receiving a radiogram (message) warning him not to ignore "Zodiac". His briefcase mysteriously disappears. Charlie meets with Deputy Police Chief J.J. Kilvaine, and runs into reporter and old friend Peter Lewis. Charlie also meets noted local magician Fred Rhadini, and discusses Essex's death with the three men. Rhadini tells Charlie about Dr. Zodiac, a psychic preying on the rich in San Francisco. Charlie, Rhadini, and Lewis go to Dr. Zodiac's home, where Dr. Zodiac conducts an eerie séance. Lewis' fiancée, Eve Cairo, has been meeting with Dr. Zodiac, angering Lewis. Later, Kilvaine reveals that Essex was poisoned, but can't rule out suicide. Jimmy spends the afternoon following Thomas Gregory, whom he believes stole Essex's briefcase when leaving the plane. He discovers Essex's manuscript in Gregory's hotel room.
Charlie Chan must stop a spy from destroying the Panama Canal, trapping a Navy fleet on its way to the Pacific after maneuvers in the Atlantic. As the U.S. fleet prepares to navigate the waters of the Panama Canal, Panama City becomes rife with spies.
The famed detective seeks to unmask a killer on a voyage across the Pacific Ocean.
Chan's testimony results in a death sentence for convicted murderer Steve McBirney (Marc Lawrence). However, he escapes and heads to a wax museum, a secret Mob hideout run by Dr. Cream (C. Henry Gordon). Cream, a crooked "facial surgeon", operates on McBirney, changing his appearance.
In the beginning of the film, detective Charlie Chan is in Rio de Janeiro, Brazil, along with his son, Jimmy, and the Rio chief of police, Chief Souto, to arrest singer Lola Dean, whom Chan suspects killed a man in Honolulu. After a performance, Lola’s boyfriend, Carlos, asks her to marry him, which she accepts. Her personal assistant, Helen Ashby, then reminds Lola she has an appointment with a Hindu psychic, Marana. Lola visits the psychic, who puts her in a semi-comatose state using coffee and cigarettes laced with a special natural herb. Lola reveals in this state that she did kill a man, Manuel Cardozo, after he refused to marry her in Honolulu. The psychic records the conversation. When Lola wakes up, the psychic tells her what she told him, but assures her that it will be kept confidential between them. On the way home, a worried Lola convinces Carlos to elope instead of marry at a later date. When she arrives home, she begins packing.
In the two years since the last Charlie Chan feature film (''Castle in the Desert''), Charlie Chan is now an agent of the U.S. government working in Washington DC and he is assigned to investigate the murder of the inventor of a highly advanced torpedo. Aiding Chan is his overeager but dull-witted Number Three son Tommy (Benson Fong) and his Number Two Daughter Iris Chan (Marianne Quon). Also involved in the case is the bumbling and easily frightened Birmingham Brown (Mantan Moreland) who works as a limo driver for one of the suspects.
Mr. Manning is murdered in his study while the door is locked from the inside. Police close the case after 6 months. A girl contacts Charlie Chan to have a look before he leaves in 48 hours. Twins are involved in a diamond-smuggling ring after the Kohinoor Diamonds are stolen; one twin is killed and the other living twin masquerades as a ghost tricking Birmingham Brown. Mr. Manning had the largest stone stored in the secret compartment of a Chinese cat statue, and doublecrossed his associates. Movie ends in a carnival funhouse with police arresting the diamond-smuggling ring for three murders. Rival author of ''Manning Murder Solved'' book must now pay $20,000 to Chinese War Relief after a lost bet with Charlie Chan about the murderer's identity.
Charlie postpones his trip home from service with the government to Honolulu to help with the investigation of murder involving Number One Daughter (Frances Chan) and an easily spooked chauffeur (Mantan Moreland).
Charlie Chan and his son Tommy and their block-head driver Birmingham Brown investigate the shenanigans and suspects that results from a furtive gang trying to steal radar secrets from a Radio broadcasting.
Aboard an ocean liner in the South Pacific, United States Department of the Treasury agent Scott Pearson confidentially asks Charlie Chan for help. There have been two attempts on his life. Chan rescues him from a third, but not the fourth (a knife in the back). The captain asks Chan to complete the dead man's mission and find out who is responsible for the recent surfacing of counterfeit dollars and stolen art. Chan declines, citing urgent business in Australia, but sets out to find the murderer.