The book features a mad scientist, De Selby, who tries to destroy the world by removing all the oxygen from the air. He has also many strange inventions. He exploits the theory of relativity and invents a kind of time travelling machine, which he uses to age his whiskey, creating brews that have been aged for many decades in just a few hours.
Saint Augustine and James Joyce both have speaking parts in the novel. James Joyce, after forging his own obituary to escape being drafted to fight in the Second World War, was serving pints in a small pub. Saint Augustine, on the other hand, appeared in a magical underwater cave and held a conversation with De Selby. The mad scientist De Selby leads the two main characters, Hackett and Mick, to the cave, to witness this conversation.
Many prominent elements of the book, particularly De Selby himself, the eccentric policemen, and the atomic theory of the bicycle, were taken from O'Brien's much earlier novel The Third Policeman, because he had not been able to find a publisher for it. The latter novel was published posthumously.
The Dalkey Archive was adapted for the stage in 1965 by Hugh Leonard as The Saints Go Cycling In