The series takes place in Toronto starting in 1895 and follows Detective William Murdoch (Yannick Bisson) of the Toronto Constabulary, who solves many of his cases using methods of detection that were unusual at the time. These methods include fingerprinting (referred to as "finger marks" in the series), blood testing, surveillance, and trace evidence.[3]

Some episodes feature anachronistic technology whereby Murdoch sometimes uses the existing technology of his time to improvise a crude prototype of a technology that would be more readily recognizable to the show's 21st-century audience. In one episode, for instance, he creates a primitive version of sonar to locate a sunken ship in Lake Ontario. In still another, a foreign police officer has a photograph that Murdoch needs as evidence, so Murdoch asks the other officer to overlay the photograph with a grid numerically coded for the colour in each square, and to transmit the numerical data to Murdoch via telegraph—with the end result that the foreign officer has essentially sent Murdoch a bitmap image they call a "facsimile"—a telefax. This aspect of the show has been described as introducing elements of the steampunk genre of science fiction,[4] although it is not a standard theme of all episodes.

Detective Murdoch is assisted by the three other main characters: Inspector Brackenreid (Thomas Craig), Doctor Julia Ogden (Hélène Joy), and the inexperienced but eager Constable George Crabtree (Jonny Harris), who aspires to be a mystery novel writer. Brackenreid, Murdoch's immediate superior, is a blunt and sceptical Yorkshireman with a fondness for whisky who 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