“The Cask of Amontillado” has one of the most straightforward plot lines of all of Poe's tales, though much of the story's detail raises questions left unanswered and mysteries that are unexplained.

The tale begins with the narrator, a man named Montresor, telling us he has suffered a “thousand injuries” from his friend Fortunato. Now that Fortunato has added “insult” to these injuries, Montresor has finally decided to seek vengeance. Montresor appears to be addressing his narrative to a particular individual, for he refers to his reader, or auditor, as “you who know me so well.” The setting is an unnamed Italian town during Carnival season. Though the period in which the story takes place is not made explicit, probably it is some time in the past. Montresor meets Fortunato at night, while the festivities are going on, and tells him that he has a “pipe” (a large amount, approximately five hundred liters) of Amontillado, a type of wine, which he wants Fortunato to taste and verify the identity of. Fortunato is dressed in “motley,” a traditional jester's costume for Carnival that includes a cap adorned with jingling bells. He already appears to be drunk. Evidently Amontillado is such an unusual wine that Fortunato doesn't at first believe Montresor that he has secured a quantity of it. Montresor suggests that another man, named Luchesi, can try the wine, but Fortunato asserts that Luchesi isn't a true connoisseur and wouldn't know Amontillado from sherry. He can't turn down the opportunity to sample the Amontillado and agrees to go with Montresor to Montresor's palazzo, where the wine is stored in his cellars, which also happen to be the catacombs where the bones of Montresor's ancestors are buried.

Though Montresor asserts that when it comes to other areas of expertise, such as painting and gemmary, Fortunato is, “like most Italians,” a quack, he acknowledges that Fortunato is in fact knowledgeable about wines, as Montresor himself is. Interestingly, Montresor specifically refers to “Italian wines” as their specialty, though Amontillado is a Spanish wine. One also has to note that while the setting is Italy, Montresor is not an Italian name, though the estate that his family has held for generations is there, in Italy.

Montresor, telling the reader that his servants will not be at the house precisely because he has ordered them not to leave, leads Fortunato on. They descend to the catacombs and go through several passageways, stopping to sample other wines, a Medoc and a De Grave, on the way to the place where the Amontillado is stored. Fortunato observes that a “white web-work” coats the walls of the damp cavern, which Montresor tells him, in answer to his guess, is nitre. Fortunato is seized by a severe fit of coughing, which seems inwardly to evoke Montresor's sympathy despite his intention to avenge himself. The two men digress for a few moments, with Montresor describing his family's extensive lineage and its coat of arms, a human foot crushing a serpent with the motto Nemo me impune lacessit, “No one harms me with impunity.” The subject of freemasonry arises when Fortunato makes a symbolic gesture that Montresor does not understand. Montresor nevertheless claims he belongs to the secret order of freemasons, despite Fortunato's doubts, and as apparent proof of it Montresor reveals a trowel, a mason's tool he has been carrying with him under his coat. This is the tool he will use in carrying out his revenge.

Eventually the two men come to a back chamber where there is a niche in the bone-lined walls. On the rear wall of the niche are two iron clamps with a suspended chain. Before Fortunato even knows what is happening, Montresor has quickly chained the drunken man into the clamps. Montresor uncovers a hidden store of building stones and mortar, and withdrawing the trowel from under his coat, he proceeds to wall up Fortunato within the niche, his intention revealed as one of burying his “friend” alive within the catacombs.

Fortunato is now apparently no longer drunk. He begins to scream but in the end only very briefly pleads in any articulate fashion for Montresor to spare his life. At first pretending to think that Montresor is playing a joke upon him, Fortunato suggests that he and Montresor return to the Carnival revelry and meet with Lady Fortunato. Finally he cries, “For the love of God, Montresor!” The avenger is not deterred, however, and secures the last stone after dropping a torch into the niche. With Fortunato now walled up in this makeshift tomb, Montresor has completed his quest for vengeance, and he tells the reader that Fortunato's body has been there undisturbed and undiscovered for fifty years. Montresor's last sentence is an ironic Latin phrase, in pace requiescat: “rest in peace.”