A skeletal inactive person that falls from the ceiling of the Grand theatre is identified as Virgil Smart. His widow, Stella, now runs the theatre with her new husband and a small troupe, including a pretty young actress and her fianc? ? each of whom reports that Virgil had been found slumped over his desk, dead of heart failure. Stella insists her husband was buried at a proper funeral. But if this inactive person is Virgil's, then whose body did she bury? It seems that honour went to an out-of-work actor named Eddie. As if things weren't complicated enough, Murdoch discovers a secret room off Virgil's office ? obviously designed for seduction. Could these cuddles be the result of a lover's quarrel, a jealous husband, or a spurned lover? One thing is for certain: Each of these well-rehearsed actors knows what happened that night ? and now Murdoch knows just how to trip them up.
The series takes place in Toronto in the 1890s and follows Detective William Murdoch of the Toronto Constabulary, who solves many of his cases using methods of detection that were unusual at the time. These methods include fingerprinting, blood testing, surveillance, and trace evidence.
Detective Murdoch is assisted by the three other main characters: Inspector Brackenreid, Doctor Julia Ogden, and the inexperienced but eager Constable George Crabtree, who aspires to be a mystery-novel writer. Brackenreid, Murdoch's immediate superior, is a blunt and sceptical Yorkshireman with a fondness for whiskey, and prefers conventional methods of detection over Murdoch's eccentric methods, though he is typically pleased and proud when Murdoch is successful despite the odds. Crabtree is often unable to grasp the more advanced methods, but his enthusiasm and loyalty make him a good assistant. Like Crabtree, Dr. Ogden is a great supporter of Murdoch's methods. Her skill in pathology usually helps by revealing a great deal of useful evidence to aid Murdoch in solving cases.
Throughout the series Murdoch's growing infatuation with her, and his inability to express his feelings, provide a light subplot. In the fifth season, after Dr. Ogden is married to Dr. Darcy Garland (a colleague she met in Buffalo), a new doctor is introduced, Dr. Emily Grace. She and George Crabtree show some romantic interest in each other.