The book comprises a preface, 25 chapters, and an afterword, with a total of around 72,000 words.
On board the Ariel (Chapter I)
Arthur Gordon Pym was born on the island of Nantucket, famous for its fishing harbor and whaling. His best friend, Augustus Barnard, is the son of the captain of a whaling ship. One night, the two boys become drunk and decide, on Augustus's whim, to take advantage of the breeze and sail out on Pym's sailboat, the Ariel. The breeze, however, turns out to be the beginnings of a violent storm. The situation gets critical when Augustus passes out drunk, and the inexperienced Pym must take control of the dinghy. The Ariel is overtaken by the Penguin, a returning whaling ship. Against the captain's wishes, the crew of the Penguin turns back to search for and rescue both Augustus and Pym. After they're safely back on land, they decide to keep this episode a secret from their parents.
On board the Grampus (Chapters II – XIII)
His first ocean misadventure does not dissuade Pym from sailing again; rather, his imagination is ignited by the experience. His interest is further fueled by the tales of a sailor's life that Augustus tells him. Pym decides to follow Augustus as a stowaway aboard the Grampus, a whaling vessel commanded by Augustus's father that is bound for the southern seas. Augustus helps Pym by preparing a hideout in the hold for him and smuggling Tiger, Pym's faithful dog, on board. Augustus promises to provide Pym with water and food until the ship is too far from shore to return, at which time Pym wants to reveal himself.
Due to the stuffy atmosphere and vapors in the dark and cramped hold, Pym becomes increasingly comatose and delirious over the days. He can't communicate with Augustus, and the promised supplies fail to arrive, so Pym runs out of water. In the course of his ordeal, he discovers a letter written in blood attached to his dog Tiger, warning Pym to remain hidden, as his life depends on it.
Augustus finally sets Pym free, explaining the mysterious message, as well as his delay in retrieving his friend: a mutiny had erupted on the whaling ship. Part of the crew was slaughtered by the mutineers, while another group, including Augustus's father, were set adrift in a small boat. Augustus survived because he had befriended one of the mutineers, Dirk Peters, who now regrets his part in the uprising.
Peters, Pym, and Augustus hatch a plan to seize control of the ship: Pym, whose presence is unknown to the mutineers, will wait for a storm and then dress in the clothes of a recently dead sailor, masquerading as a ghost. In the confusion sure to break out among the superstitious sailors, Peters and Augustus, helped by Tiger, will take over the ship again. Everything goes according to plan, and soon the three men are masters of the Grampus: all the mutineers are killed or thrown overboard except one, Richard Parker, whom they spare to help them run the vessel.
The storm increases in force, breaking the mast, tearing the sails and flooding the hold. All four manage to survive by lashing themselves to the hull. As the storm abates, they find themselves safe for the moment, but without provisions. Over the following days, the men face death by starvation and thirst.
They sight an erratically moving Dutch ship with a grinning red-capped seaman on deck, nodding in apparent greeting as they approach. Initially delighted with the prospect of deliverance, they quickly become horrified as they are overcome with an awful stench. They soon realize that the apparently cheerful sailor is, in fact, a corpse propped up in the ship's rigging, his "grin" a result of his partially decomposed skull moving as a seagull feeds upon it. As the ship passes, it becomes clear that all its occupants are rotting corpses.
As time passes, with no sign of land or other ships, Parker suggests that one of them should be killed as food for the others. They draw straws, following the Custom of the Sea and Parker is sacrificed. This gives the others a reprieve, but Augustus soon dies from wounds received when they reclaimed the Grampus, and several more storms batter the already badly damaged ship. Pym and Peters float on the upturned hull and are close to death when they are rescued by the Jane Guy, a ship out of Liverpool.
On board the Jane Guy (Chapters XIV – XX)
On the Jane Guy, Pym and Peters become part of the crew and join the ship on its expedition to hunt sea calves and seals for fur, and to explore the southern oceans. Pym studies the islands around the Cape of Good Hope, becoming interested in the social structures of penguins, albatrosses, and other sea birds. Upon his urging, the captain agrees to sail further south towards the unexplored Antarctic regions.
The ship crosses an ice barrier and arrives in open sea, close to the South Pole, albeit with a mild climate. Here the Jane Guy comes upon a mysterious island called Tsalal, inhabited by a tribe of black, apparently friendly natives led by a chief named Too-Wit. The color white is alien to the island's inhabitants and unnerves them, because nothing that color exists there. Even the natives' teeth are black. The island is also home to many undiscovered species of flora and fauna. Even its water is different from water elsewhere, being strangely thick and exhibiting multicolored veins.
The natives' relationship with the sailors is initially cordial, so Too-Wit and the captain begin trading. Their friendliness, however, turns out to be a ruse and on the eve of the ship's proposed departure, the natives ambush the crew in a narrow gorge. Everyone except Pym and Peters is slaughtered, and the Jane Guy is overrun and burned by the malevolent tribe.
Tsalal and further south (Chapters XXI – XXV)
Pym and Peters hide in the mountains surrounding the site of the ambush. They discover a labyrinth of passages in the hills with strange marks on the walls, and disagree about whether these are the result of artificial or natural causes. Facing a shortage of food, they make a desperate run and steal a pirogue from the natives, narrowly escaping from the island and taking one of its inhabitants prisoner.
The small boat drifts further south on a current of increasingly warm water, which has become milky white in color. After several days they encounter a rain of ashes and then observe a huge cataract of fog or mist, which splits open to accommodate their entrance upon approach. The native dies as a huge shrouded white figure appears before them.
Here the novel ends abruptly. A short post-script, ostensibly written by the book's editors, compares the shapes of the labyrinth and the wall marks noted by Pym to Arabian and Egyptian letters and hieroglyphs with meanings of "Shaded", "White", and "Region to the South".