In the story, the brilliant consulting detective Sherlock Holmes is asked to investigate the disappearance of the ten-year-old son of the Duke of Holdernesse. The boy went missing from a prestigious private boarding school in the north of England a few days earlier. A teacher is known to have gone missing from the school at the same time, although what connection he has with the boy's disappearance is unclear. The case is further complicated when the teacher is found dead. The teacher is found on damp marshland, having obviously been savagely beaten by a man. However, the only tracks visible near his body are those of cows.

Sir Arthur Conan Doyle included "The Adventure of the Priory School" in a list of his twelve favorite Sherlock Holmes short stories which he compiled for The Strand magazine in 1927.