In Island of the Blue Dolphins, a young native American girl named Karana witnesses her life change forever when a ship of an enemy tribe lands on her island. After a tumultuous time of conflict and change, Karana and her brother are the only ones left on the island. When her brother dies, Karana must make a life for herself. Her many trials and long years of solitude tell a story about the path to morality, forgiveness, and the importance of human connection.
The main character is a girl named Karana. She has a brother named Ramo, whose curiosity usually leads to trouble, and a sister named Ulape. Her people live in a village called Ghalas-at and the tribe survives by means of gathering roots and fishing.
One day, a ship of Russian fur hunters and Aleut people led by Captain Orlov arrive and persuade the natives to let them hunt sea otter in exchange for other goods. However, the Russians attempt to swindle the islanders and leave without paying. When they are confronted by Karana's father Chief Chowig, a battle breaks out. The tribe is greatly reduced with Karana's father and many other men in the tribe dying in battle against the well-armed Russians who escape largely unscathed.
Later, the "replacement chief" Chief Kimki leaves the island on a canoe for new land in the East. Eventually, he sends a "giant canoe" to bring his people to the mainland even though he himself does not return. The white men who are missionaries come to Karana's village and tell them to pack their goods and go to the ship. Karana's brother Ramo misses the ship to retrieve his fishing spear. Although Karana urges the captain to wait for Ramo to return, the ship must leave before a storm approaches. Despite restraint, Karana jumps off the ship and swims to shore and the ship departs without them.
The siblings live alone on the island, hoping the ship will return. However, Ramo is brutally killed by a pack of feral dogs. Alone on the island, Karana takes on traditionally male tasks, such as hunting, making spears, and building canoes to survive. She vows to avenge her brother's death and kills several of the dogs, but has a change of heart when she encounters the leader of the pack. She tames him and names him Rontu (meaning "Fox Eyes" in her language).
Over time, Karana makes a life for herself. She builds a home made of whale bones and stocks a cave with provisions in case the Aleuts come back, so she can hide from them. As she explores her island, Karana discovers ancient artifacts and a large squid (which she calls a devilfish). As time passes, she decides to hunt the devilfish. She also tames some birds and an otter while feeling a close kinship to the animals (the only inhabitants of the island beside herself).
One summer, the Aleuts return and Karana takes refuge in the cave. She observes the Aleuts closely and realizes that a girl named Tutok takes care of the domestic duties including getting water from the pool near Karana's cave. Fearful of being discovered, Karana goes out only at night, yet the curious girl stalks Karana and the two meet. Karana and Tutok meet several days in a row. However, when she lets Rontu out with her, Tutok calls him hers. Karana and Tutok exchange gifts, and she realizes how lonely she's been. Karana wishes that Tutok would not leave, yet the next day when Karana makes food for her she doesn't come. Karana goes searching and sees the ship departing. Sadly, she returns to her house and starts rebuilding.
More time passes and Rontu dies. Karana soon finds a young dog that looks like Rontu and takes him in naming him Rontu-Aru (meaning "Son of Rontu"). One day, Karana sees the sails of a ship. It docks at the shore, but then leaves. Two years later in the spring, the boat comes back, so Karana dresses in her finest attire and goes to the shore to meet the boat. Her rescuers see that her dress made of cormorant feathers is not appropriate for the mainland and they have a dress made for her. She does not like the dress, but Karana realizes that it is part of her new life. The ship takes Karana and Rontu-Aru to the mission in Santa Barbara, California. There, she finds out that the ship that had taken her people away had sunk, before it could return from the mainland for her.