Ed befriends the daughter of the judge presiding over his latest case, only for the girl to come to him in fear for her father's life. It seems she is overreacting to a series of accidents, but events soon suggest her suspicions may be correct; especially after it turns out that her father's new wife has old Underworld connections she thought she had left behind.
A British police inspector visits San Francisco for a conference, and whilst there assists his old friend Chief Ironside with an awkward investigation. It soon appears, however, that he knows more about the case than he should do, and that his involvement may have something to do with his deteriorating state of health.
Peter Justin, a gentleman jewel thief and old adversary of the Chief's, returns from a five year stretch in San Quentin and is soon back to his old life. When a protégé frames him for a robbery and murder charge the Chief has to prove him innocent, despite his knowledge that another recent robbery is most definitely the work of Justin alone.
After the killing of one of his men, gangland boss Lew Parker puts out a contract on Ironside, which the undercover Ed is forced to pick up. Unable to contact the rest of the team Ed has to go along with the preparations for a heist, but when his cover is blown and he winds up a prisoner, the Chief and co must find the missing links before it is too late.
Mark and his girlfriend come across a murder whilst on a date, but decide to defend the killer when it transpires that he acted in self defence. During the case the pair get married, and Ed decides to move in with the Chief in Mark's place.
A woman is killed in a locked room, and her daughter Susan confesses to the murder after apparently becoming possessed by the spirit of her long-dead younger brother. The Chief enlists a psychic to help him in his investigations, but the clues that she offers him seem to confuse more than they assist.
When an assassin's bullet confines him to a wheelchair for life ending his career as Chief of Detectives, Robert T. Ironside becomes a consultant to the police department. Detective Sergeant Ed Brown and policewoman Eve Whitfield join with him to crack varied and fascinating cases. Ex-con Mark Sanger is employed by the chief as home help but eventually becomes a fully fledged member of the team also. Officer Whitfield leaves after 4 years service, and is replaced by Officer Fran Belding.