Cora and Alice Munro, daughters of Lieutenant Colonel Munro, are traveling with Major Duncan Heyward from Fort Edward to Fort William Henry, where Munro is in command, and acquire another companion in David Gamut, a singing teacher. They are guided through the forest by a native named Magua, who leads them through a shortcut unaccompanied by the British militia. Heyward is dissatisfied with Magua's shortcut, and the party roams unguided and finally join Natty Bumppo, known as Hawk-eye, a scout for the British, and his two Mohican friends, Chingachgook and his son Uncas. Heyward becomes suspicious of Magua, and Hawk-eye and the Mohicans agree with his suspicion that Magua is a Huron scout secretly allied with the French. Upon discovery as such, Magua escapes, and in the (correct) belief that Magua will return with Huron reinforcements, Hawk-eye and the Mohicans lead their new companions to a hidden cave on an island in a river. They are attacked there by the Hurons, and their ammunition is soon exhausted. Knowing they will be killed instantly but that the English party will make valuable captives, Hawk-eye and the Mohicans escape, with a promise to return for their companions.
Magua and the Hurons capture Heyward, Gamut, and the Munro sisters. Magua admits that he is seeking revenge against Cora's father, Colonel Munro, for turning him into an alcoholic with whiskey (causing him to be temporarily cast out of the Hurons) and then whipping him at a post for drunken behavior. He offers to spare the party if Cora becomes his wife, but she refuses. Upon a second refusal, he sentences the prisoners to death. Hawk-eye and the Mohicans rescue all four and lead them to a dilapidated building that was involved in a battle between the Huron and the British some years ago. They are nearly attacked again, but the Hurons leave the area, rather than disturb the graves of their tribesmen.
The next day, Hawk-eye leads the party to Fort Henry, past a siege by the French army. Munro sends Hawk-eye to Fort Edward for reinforcements, but he is captured by the French, who deliver him to Fort Henry without the letter. Heyward returns to Colonel Munro and announces his love for Alice, and Munro gives his permission for Heyward's courtship. The French general, Montcalm, invites Munro to a parley and shows him General Webb's letter, in which the British general has refused reinforcements. At this, Munro agrees to Montcalm's terms: that the British soldiers, together with their women and children, must leave the fort and withdraw from the war for eighteen months. Outside the fort, the column of British evacuees is betrayed and ambushed by 2,000 Huron warriors; in the ensuing massacre, Magua kidnaps Cora and Alice, and he leads them toward the Huron village, with David Gamut in pursuit.
Hawk-eye, the Mohicans, Heyward, and Colonel Munro survive the massacre and set out to follow Magua, and cross a lake to intercept his trail. They encounter a band of Hurons by the lakeshore, who spot the travelers. A canoe chase ensues, in which the rescuers reach land before the Hurons can kill them, and eventually follow Magua to the Huron village. Here, they find Gamut (earlier spared by the Hurons as a harmless madman), who says that Alice is held in this village and Cora in one belonging to the Lenape (Delaware).
Disguised as a French medicine man, Heyward enters the Huron village with Gamut to rescue Alice; Hawk-eye and Uncas set out to rescue Cora, and Munro and Chingachgook remain in safety. Uncas is taken prisoner by the Hurons and left to starve when he withstands torture, and Heyward fails to find Alice. A Huron warrior asks Heyward to heal his lunatic wife, and both are stalked by Hawk-eye in the guise of a bear. They enter a cave where the madwoman is kept, and the warrior leaves. Soon after the revelation of his identity to Heyward, Hawk-eye accompanies him, and they find Alice. They are discovered by Magua, but Hawk-eye overpowers him, and they leave him tied to a wall. Thereafter Heyward escapes with Alice, while Hawk-eye remains to save Uncas. Gamut convinces a Huron to allow him and his magical bear (Hawk-eye in disguise) to approach Uncas, and they untie him. Uncas dons the bear disguise, Hawk-eye wears Gamut's clothes, and Gamut stays in a corner mimicking Uncas. Uncas and Hawk-eye escape by traveling to the Delaware village where Cora is being held, just as the Hurons suspect something is amiss and find Magua tied up in the cave. Magua tells his tribe the full story behind Heyward and Hawk-eye's deceit before assuming leadership of the Hurons, who vow revenge.
Uncas and Hawk-eye are being held prisoner with Alice, Cora, and Heyward by the Delawares. Magua enters the Delaware village and demands the return of his prisoners. During the ensuing council meeting, Uncas is revealed to be a Mohican, a once-dominant tribe closely related to the Delawares. Tamenund, the sage of the Delawares, sides with Uncas and frees the prisoners, except Cora, whom he awards to Magua according to tribal custom. This makes a showdown between the Hurons and Delawares inevitable, but to satisfy laws of hospitality, Tamenund gives Magua a three-hour head start before pursuit. While the Delawares are preparing for battle, David Gamut escapes the Huron village and tells his companions that Magua has positioned his men in the woods between the Huron and Delaware villages. Undeterred, Uncas, Hawk-eye, Heyward, Gamut, and the Delawares march into the woods to fight the Hurons.
In the ensuing battle, the Delawares are joined by Chingachgook and Munro, and ultimately vanquish the Hurons and capture their village, but Magua escapes with Cora and two other Hurons; Uncas, Hawk-eye, Heyward, and Gamut pursue them up to a high mountain. In a fight at the edge of a cliff, one of the Hurons kills Cora, Gamut kills one of the Hurons, Magua kills Uncas, and Hawk-eye kills Magua. The novel concludes with a lengthy account of the funerals of Uncas and Cora at the Delaware village, and Hawk-eye reaffirms his friendship with Chingachgook. Tamenund prophesies: "The pale-faces are masters of the earth, and the time of the red-men has not yet come again..."
