The narrator of this novel, fifteen-year-old Christopher Boone, is autistic (or, more accurately, probably, has Asperger's Syndrome). He lives with his father and believes his mother died two years before. Christopher is extremely good at mathematics, seems to have a photographic memory, but does not like novels (other than detective stories, which are about observation and logic), because he cannot empathize with human emotions or make sense of the indirect or figurative. For Christopher, metaphors, like fictions, are lies. He is very fond of dogs, and hates to be touched by people.

When a neighbour's dog is killed, he decides to investigate and, with the encouragement of his teacher, to write a book about his investigation. He quickly makes some very disturbing discoveries. He learns that his mother is not dead after all, but living in London with the husband of the dead dog's owner. The fact that his father has lied to him devastates Christopher. He runs away to London to find his mother, and his courage and tenacity allow him to solve not only the mystery of the dog's death but that of his family's past and future.