A five-year-old girl, who readers come to understand is Cro-Magnon, is orphaned and left homeless by an earthquake that destroys her family's camp. She wanders aimlessly, naked and unable to feed herself, for several days. Having been attacked and nearly killed by a cave lion and suffering from starvation, exhaustion, and infection of her wounds, she collapses, on the verge of death.
The narrative switches to a group of people who call themselves "The Clan" and who we come to understand are Neanderthal, whose cave was destroyed in the earthquake and who are searching for a new home. The medicine woman of the group, Iza, discovers the girl and asks permission from Brun, the head of the Clan, to help the ailing child, despite the child being clearly a member of "the Others", the distrusted antagonists of the Clan. The child is adopted by Iza and her brother Creb. Creb is this group's "Mog-ur" or shaman, despite being deformed as a result of the difficult birth resulting from his abnormally large head and the later loss of an arm and eye after being attacked by a cave bear. The clan call her Ayla, the closest they can come to saying her "strange" name. After traveling with them for a while and starting to heal, Ayla wanders away from the group when they stop to discuss what they should do since they haven't found a new home and she discovers a huge, beautiful cave, perfect for them; many of the people begin to regard Ayla as lucky, especially since good fortune continues to come their way as she lives among them.
In Auel's books, the Neanderthal possess only limited vocal apparatus and rarely speak, but have a highly developed sign language. They do not laugh or even smile, and they do not cry; when Ayla weeps, Iza thinks she has an eye disease.
Ayla's different thought processes lead her to break important Clan customs, particularly the taboo against females handling weapons. She is self-willed and spirited, but tries hard to fit in with the Neanderthals, although she has to learn everything first-hand; she does not possess the ancestral memories of the Clan which enable them to do certain tasks after being shown only once.
Iza trains Ayla as a medicine woman "of her line", the most prestigious line of medicine women out of all of the Clans. It takes her much longer to train Ayla than it will her own daughter, Uba, since Ayla does not possess the memories of the Clan. When Ayla grows up, Iza is concerned she will never find a mate and no one will want her, making her a burden to the Clan, so she trains her to be a highly respected medicine women so she will have her own "status" and will not have to rely on the status of a possibly lowly mate.
Ayla's main antagonist is Broud, son of the leader, an egomaniac who feels that she takes credit and attention away from him. As the two mature, the hatred between them festers. When they are young adults, Broud rapes Ayla, but she becomes pregnant, and rejoices in the birth of a son. Her son is almost taken away from her because he seems deformed to the Clan, since he does not look like them and, in the beginning, cannot hold up his head.
The book ends with Creb's death, Broud's succession to the leadership, and his banishment of Ayla, who sets off to find other people of her own kind. She is not allowed to take her son with her. The separation haunts her with guilt and grief for the rest of the series.