The Pearl, which takes place in La Paz, Mexico, begins with a description of the seemingly idyllic family life of Kino, his wife Juana and their infant son, Coyotito. Kino watches as Coyotito sleeps, but sees a scorpion crawl down the rope that holds the hanging box where Coyotito lies. Kino attempts to catch the scorpion, but Coyotito bumps the rope and the scorpion falls on him. Although Kino kills the scorpion, it still stings Coyotito. Juana and Kino, accompanied by their neighbors, go to see the local doctor, who refuses to treat Coyotito because Kino cannot pay. Kino and Juana leave the doctors and take Coyotito down near the sea, where Juana uses a seaweed poultice on Coyotito's shoulder, which is now swollen.
Kino dives for oysters from his canoe, attempting to find pearls. He finds a very large oyster which, when Kino opens it, yields an immense pearl. Kino puts back his head and howls, causing the other pearl divers to look up and race toward Kino's canoe. The news that Kino has found an immense pearl travels fast through La Paz. The doctor who refused to treat Coyotito decides to visit Kino.
Kino's neighbors begin to feel bitter toward him for his good fortune, but neither Kino nor Juana realize this feeling they have engendered. Juan Tomas, the brother of Kino, asks him what he will do with his money, and he envisions getting married to Juana in a church and dressing Coyotito in a yachting cap and sailor suit. He claims that he will send Coyotito to school and buy a rifle for himself. The local priest visits and tells Kino to remember to give thanks and to pray for guidance. The doctor also visits, and although Coyotito seems to be healing, the doctor insists that Coyotito still faces danger and treats him.
Kino tells the doctor that he will pay him once he sells his pearl, and the doctor attempts to discern where the pearl is located (Kino has buried it in the corner of his hut). That night, a thief attempts to break into Kino's hut, but Kino drives him away. Juana tells Kino that the pearl will destroy them, but Kino insists that the pearl is their one chance and that tomorrow they will sell it. Kino's neighbors wonder what they would do if they had found the pearl, and suggest giving it as a present to the Pope, buying Masses for the souls of his family, and distributing it among the poor of La Paz. Kino goes to sell his pearl, accompanied by his neighbors, but the pearl dealer only offers a thousand pesos when Kino believes that he deserves fifty thousand. Although other dealers inspect the pearl and give similar prices, Kino refuses their offer and decides to go to the capital to sell it there.
That night, Kino is attacked by more thieves, and Juana once again reminds Kino that the pearl is evil. However, Kino vows that he will not be cheated, for he is a man. Later that night, Juana attempts to take the pearl and throw it into the ocean, but Kino finds her and beats her for doing so. While outside, a group of men accost Kino and knock the pearl from his hand. Juana watches from a distance, and sees Kino approach her, limping with another man whose throat Kino has slit. Juana finds the pearl, and they decide that they must go away even if the murder was in self-defense.
Kino finds that his canoe has been damaged and their house was torn up and the outside set afire. Kino and Juana stay with Juan Tomas and his wife, A polonia, where they hide for the next day before setting out for the capital that night. Kino and Juana travel that night, and rest during the day. When Kino believes that he is being followed, the two hide and Kino sees several bighorn sheep trackers who pass by him. Kino and Juana escape into the mountains, where Juana and Coyotito hide in the cave while Kino, taking his clothes off so that no one will see his white clothing. The trackers think that they hear something when they hear Coyotito crying, but decide that it is merely a coyote pup.
After a tracker shoots in the direction of the cries, Kino attacks the three trackers, killing all three of them. Kino can hear nothing but the cry of death, for he soon realizes that Coyotito is dead from that first shot. Juana and Kino return to La Paz. Kino carries a rifle stolen from the one of the trackers he killed, while Juana carries the dead Coyotito. The two approach the gulf, and Kino, who now sees the image of Coyotito with his head blown off in the pearl, throws it into the ocean..