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 naiive 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 roam unguided and finally join Natty Bumppo (known as Hawk-eye), a British scout, 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 when ammunition is exhausted, Hawk-eye and the Mohicans escape, with a promise to return for their companions. At length, Magua and Hurons capture Heyward, Gamut, and the Munro sisters, and Magua offers to spare the party if Cora becomes his wife; but she refuses. Upon a second refusal, he sentences the prisoners to death; but Hawk-eye and the Mohicans rescue all four, and lead them to a dilapidated building. They are nearly attacked again; but the Hurons leave them unharmed, rather than disturb the graves of their own fellow-countrymen. 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 William 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 wounded, women, and children, must leave the fort and withdraw from the war for eighteen months. Outside the fort, the column of British prisoners is attacked by 2000 Huron warriors; in which massacre, Magua finds Cora and Alice, and he leads them toward the Huron village. David Gamut follows. After the massacre, Hawk-eye, the Mohicans, Heyward, and Colonel Munro follow Magua, and cross a lake to intercept his trail. 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. Soon after 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 enters the bear disguise, Hawk-eye wears Gamut's clothes, and Gamut stays in a corner mimicking Uncas. Uncas and Hawk-eye escape and the Hurons vow revenge.

Uncas, Heyward, Alice, and Hawk-eye travel to the Delaware village where Cora is held, and where Magua demands the return of his prisoners. Tamenund, the sage of the Delawares, frees the prisoners, except for Cora, whom he awards to Magua. To satisfy laws of hospitality, Tamenund gives Magua a three-hour head start before pursuit. The Delawares vanquish the Hurons, but Magua escapes with Cora and two other Hurons; Uncas, Hawk-eye, and Heyward pursue them. In a fight at the edge of a cliff, Cora, Uncas, and Magua are killed. The novel concludes with a lengthy account of the funerals of Uncas and Cora, and Hawk-eye renews 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....".