The action takes place around Glens Falls in upstate New York. Cora and Alice Munro, daughters of Lieutenant Colonel Munro, are traveling with a column of reinforcements from Fort Edward to Fort William Henry, where Munro is commanding an army. In the party are David Gamut the singing teacher, and Major Duncan Heyward, the group's military leader.
Magua, the treacherous Huron scout, offers to take the Munro party to Fort William Henry, but leads them into an ambush instead. Natty Bumppo (also known as Hawkeye) and his two Mohican friends, Chingachgook and his son Uncas, rescue them just in time. Knowing that Magua (also known as Le Renard Subtil, the cunning fox) will soon return with reinforcements, Hawkeye and the Mohicans lead their new companions to a nearby cave. A group of Hurons sent by Magua chase them into the cave. After a fierce struggle, Hawkeye and his friends decide to split up for safety, with Hawkeye and the Mohicans hiding in a nearby stream, while Heyward, Gamut, and the Munro sisters retreat back into the cavern.
Magua returns with more Hurons and captures Cora, Alice and the two men in the cave. The Hurons take their captives to a stream with mineral water, where they rest briefly while watchful of the others. The Hurons interrogate Heyward, who tells them that Hawkeye and the Mohicans have escaped and learns from them that Uncas's nickname is the Bounding Elk and that Hawkeye is referred to as the Long Rifle or La Longue Carabine.
When Cora demands why the Hurons were so eager to capture them, Magua tells his captives that Colonel Munro and other white officers came to the Huron village one day and introduced him to fire-water (whiskey) and his drunken misbehavior caused the Hurons to expel him from the tribe. He subsequently allied himself with the Mohawks (allies of the British) and went to war with them against the French and their Huron allies. Magua continued to drink the fire-water during the fighting and after one act of disorder, Munro ordered him tied to a post and whipped, wounding him both physically and spiritually. He has since gone back to the Hurons and is seeking revenge against Munro. He offers to spare the others in return for Cora following him to the Huron village as his wife, but Cora flatly refuses.
Hawkeye, Uncas, and Chingachgook surprise the Hurons and kill most of them with Heyward's assistance, but Magua escapes once more. Hawkeye tells the former hostages that they had been secretly trailing the Hurons after their capture. After a short chase they decided to take action after the Hurons threatened to kill the captives. Heyward and Hawkeye lead the Munro women to Fort William Henry, which is by now surrounded by the French.
Munro sends Hawkeye to Fort Edward to request reinforcements but, bearing General Webb's reply, he is captured by the French, who deliver him to Fort William Henry without the letter. Heyward attempts to parley with the French, but learns nothing. He then returns to Colonel Munro and announces his love for Alice. Munro reveals Cora's heritage—the Colonel's first wife was of mixed race—then gives his permission for Heyward to pay court to Alice.
The French general, Montcalm, invites Munro to a parley. He shows him Webb's letter: the English general has refused to send further reinforcements. Realizing that his cause is lost, Munro reluctantly agrees to Montcalm's terms. The British soldiers, together with their wounded, and women and children, are allowed to leave the fort and withdraw. Outside the fort, the column is set upon by 2000 French allied Indian warriors. In the chaos of the massacre, Magua finds Cora and Alice, and leads them away towards the Huron village. David Gamut follows at a distance.
Three days later, Hawkeye and the Mohicans, Heyward and Colonel Munro enter the ruins of Fort William Henry, where they plan their next move by the council fire. The next morning they set off for Lake George on canoes where they encounter a group of Hurons and escape after a brief but intense chase. Upon reaching shore they hide the canoe and follow Magua's trail. Outside the Huron village, they come across David Gamut, teaching beavers to sing psalms. The Huron have not killed him as they will not harm a madman. Gamut tells them that Alice is in the village, Cora is in another village belonging to the Lenni Lenape (Delaware) tribe, and Magua has gone moose hunting. Heyward disguises himself as a French medicine man and enters the village with Gamut, intending to rescue Alice. Hawkeye and Uncas set out to rescue Cora. Chingachgook remains with Colonel Munro, who has become somewhat deranged as a result of events.
Heyward's disguise is successful, but before he can find Alice, Uncas is led into the village, having been captured by the Hurons. Magua returns, and demands that Uncas be put to death, but does not recognise Heyward in his guise as a medicine man. Hawkeye steals a bearskin from a village shaman and uses it to disguise himself while he follows Heyward. They rescue Alice after finding her in a cave, taking her out of the village by wrapping her in cloth and convincing the Hurons she is a sick woman Heyward, as a French medicine man, had been asked to heal of an evil spirit. As Heyward carries Alice towards the Lenni Lenape village, David Gamut and Hawkeye (still disguised in bear skin of the village shamen) return to the village to rescue Uncas. Uncas's guards recognize the bear suit and allow the two to pass, believing Gamut will perform some magic to torture Uncas. Once reunited, Uncas dons the bear skin while Hawkeye dresses as Gamut and begins to sing. Gamut stays behind while Uncus and Hawkeye pass the guards, who did not notice a different white man exited than had entered. The pair flee to the Delaware village.
The Hurons discover Gamut and realize that Uncas has escaped. When they enter the cave, they find Magua, who had been left bound and gagged by Heyward and Hawkeye as they rescued Alice. Magua tells them everything about Hawkeye's and Heyward's deception, enraging the other Hurons, who vow revenge against Hawkeye and his companions and quickly reaffirm Magua as their chief.
Magua then makes his way to the Delaware village, demands the return of his prisoners, warning that one of the white captives is La Longue Carabine, the infamous killer of natives. At the council of chiefs, the venerable sage Tamenund is called on to make the final judgement. He asks which of the prisoners is La Longue Carabine. Hawkeye initially remains silent, since he does not claim the title for himself (His weapon is a smoothbore), so Heyward, mistaking Hawkeye wishes to be undiscovered, claims he is the man in question. Hawkeye then also claims the title, explaining the delay. To resolve the issue a shooting match is organised, at which Hawkeye outshoots the Major.
Tamenund grants Magua's wish to keep his prisoners, but as she is being taken away Cora falls at the great sage's feet and begs him to reconsider. Unable to convince him to free either her sister or herself, she eventually begs him to hear her side of the story from a Delaware warrior, referring to Uncas. The tribe did not realize Uncas's heritage, and so he is summoned to speak.
Upon arrival, Uncas offends the Delaware, who tear off his clothing in preparation to beat him. They stop upon discovering a turtle tattoo on his chest, identifying his people. At this point, Tamenund accedes to all Uncas asks and frees the prisoners, except he cannot free Cora as it was Magua who brought her to the village. Magua reluctantly also agrees to Uncas's demands but announces his intention to keep Cora as his wife, spurning Hawkeye's offer to allow Magua to take him prisoner instead in exchange for releasing Cora. Uncas and Heyward both vow to hunt down and kill Magua and rescue Cora as the Huron chief leaves with his captive.
According to custom, Tamenund has agreed to give Magua a three-hour head start before permitting the Delaware to pursue in attempt to rescue Cora. As the Delawares use this time to prepare for battle and equip themselves with tomahawks and rifles, David Gamut finds his way to the Delaware village, and tells the group that he saw Magua and Cora return to the Huron village, where he sent Cora into the same cave where Heyward rescued Alice before ordering the Huron warriors into battle. With this in mind, the Delawares led by Uncas march into the forest to confront the Hurons.
A battle breaks out between the Hurons and the Delaware, who are in three parties: one led by Hawkeye and Heyward, one by Uncas, and one by Chingachgook and Munro. During the course of battle the Hurons are forced back to their village with heavy losses and ultimately are defeated when the Delaware capture the village. Magua escapes with Cora and two of his warriors with Uncas, Hawkeye, and Heyward in pursuit, and they seek to flee by a mountain path which has a precipitous drop on one side, but Cora stops on a rocky ledge and refuses to go further. Uncas attacks the Huron, but both he and Cora are killed in the fight. Hawkeye arrives too late, and shoots Magua, who then falls to his death from a nearby cliff.
The novel concludes with a lengthy account of the funerals of Uncas and Cora. The Lenni Lenape sing that Uncas and Cora will marry in the afterlife. Hawkeye does not believe this, but he renews his friendship with Chingachgook. Tamenund foresees that "The pale-faces are masters of the earth, and the time of the red-men has not yet come again...."