This remarkable book is one of the most unusual ever written. It is set in the early part of the 18th Century, and takes the form of a first-person autobiography, which mingles the naturalistic and the fantastic in the most idiosyncratic way. Most of the narrator's time is spent wandering around the Northern Pennines, where he finds valleys, caves, lakes and waterfalls which are described in detail, but are entirely imaginary. At intervals he meets with hospitable people, who invariably have marriageable daughters. These are of course, beautiful and modest, but far from being the kind of sexy flibbertigibbet usual in 18th Century fiction (think of Sophia Western in Tom Jones, for example) they are without exception highly intelligent, and often very well educated. He has long conversations with them about learned matters, in the course it comes out that they are, like him, Unitarian, or easily convinced to become so. He marries no fewer than seven of them in turn, and is widowed in each case after a short while. His sole comment on their children, however, is "they never were concerned in any extraordinary affairs, nor ever did any remarkable things, [so] it would not be fair, in my opinion, to make anyone pay for their history." Between the fourth and fifth he goes to London, where he becomes involved with the unscrupulous publisher Edmund Curll (a real person) before being stripped of all his fortune by card-sharpers. He rescues a girl from her brutal father, and returns to the North with her. What follows is even more unlikely than any of his previous adventures.
All of this is interspersed with lengthy digressions on theology, mathematics, chemistry, Greek philosophy and other abstruse subjects, in which his religious prejudices are given free rein. He condemns the bigotry of his opponents, (while being just as bad himself) and takes time out to give potted biographies of now forgotten theologians in footnotes which sometimes go on for several pages. In the opinion of William Hazlitt:
"The soul of Francis Rabelais passed into John Amory, the author of The Life and Adventures of John Buncle. Both were physicians, and enemies of too much gravity. Their great business was to enjoy life. Rabelais indulges his spirit of sensuality in wine, in dried neatsí tongues, in Bologna sausages, in botargos. John Buncle shews the same symptoms of inordinate satisfaction in tea and bread and butter. While Rabelais roared with Friar John and the Monks, John Buncle gossiped with the ladies; and with equal and uncontrolled gaiety