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, a Huron scout secretly allied with the French, leads them into an ambush. Natty Bumppo (also known as Hawkeye) and his Mohican friends, Chingachgook and his son Uncas, rescue the party. Knowing that Magua will return with reinforcements, Hawkeye and the Mohicans lead their new companions to a cave and split up for safety.
Magua returns with more Hurons and captures Heyward, Gamut, and the Munro sisters. When Cora demands to know why the Hurons were so eager to capture them, Magua says that Colonel Munro and the "Canada fathers" introduced him to firewater, causing him to get drunk and be expelled from his tribe. He allied with the Mohawks but continued to drink. After Munro had him whipped after a drunken episode, Magua returned to the Hurons and is leading them in revenge against the British. He offers to spare the party if Cora will go with him as his wife to the Huron village, but she refuses.
Hawkeye, Uncas, and Chingachgook return and ambush the Hurons, killing most of them, though Magua escapes. Heyward and Hawkeye lead the Munro women to Fort William Henry, now surrounded by the French.
Munro sends Hawkeye to Fort Edward for reinforcements. While bearing General Webb's reply, 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. Munro reveals that Cora's mother was of mixed race of African ancestry from the West Indies and gives his permission for Heyward's courtship.
The French general, Montcalm, invites Munro to a parley. He shows him Webb's letter: the British general has refused to send reinforcements. Realizing that his cause is lost, Munro agrees to Montcalm's terms. The British soldiers, together with their wounded, women, and children, are allowed to leave the fort and withdraw. Outside the fort, the column is set upon by 2000 Indian warriors. In the chaos of the massacre, Magua finds Cora and Alice, and he leads them toward the Huron village. David Gamut follows.
Hawkeye, the Mohicans, Heyward, and Colonel Munro follow Magua's trail, evading a party of native warriors. Outside the Huron village, they come across Gamut. The Huron consider him mad for all his singing and won't kill him. Gamut says that Alice is being held in this village, Cora in one belonging to the Lenape (Delaware) tribe, and Magua is hunting. Disguised as a French medicine man, Heyward enters the Huron village with Gamut, intending to rescue Alice. Hawkeye and Uncas set out to rescue Cora.
Hawkeye and Heyward rescue Alice, and then Gamut and Hawkeye team up to free the captured Uncas. The Hurons vow revenge and reaffirm Magua as their chief.
Magua demands the return of his prisoners. Tamemund, the old sage of the Delawares, frees the prisoners, except for Cora, as she belongs to Magua. Magua leaves with his captive.
Tamenund has agreed to give Magua a three-hour head start before permitting the Delaware to pursue to try to rescue Cora. As the Delaware use the extra time to prepare for battle, Gamut arrives. He said he saw Magua and Cora at the Huron village, and she was hidden in the cave where they earlier found Alice. The Delaware go to confront the Huron and force the Huron back, taking the village. Magua escapes with Cora; Uncas, Hawkeye, and Heyward pursue them through the mountains. When Uncas attacks the Huron, he and Cora are killed. Hawkeye arrives and shoots Magua, who falls to his death from a cliff.
The novel concludes with a lengthy account of the funerals of Uncas and Cora. Hawkeye 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...."