The Catholic detective William Murdoch (Yannick Bisson) solves his cases in Protestant Toronto at the turn of the century in a highly unconventional way for his time: with the help of fingerprints, blood samples, precise analysis and searches for clues at the crime scene, he always succeeds in convicting the guilty party or parties, sometimes much to the astonishment of his superiors. With the help of his subordinate Constable George Crabtree (Jonny Harris) and the forensic pathologist Julia Ogden (Hélène Joy), Murdoch achieves successes that ultimately even convince Inspector Brackenreid (Thomas Craig) of his abilities.