Gower, an offscene narrator, enters to tell about the kingdom of Antioch, where king Antiochus and Antiochus's daughter are engaging in incest. Antiochus has kept suitors from marrying her by requiring that they answer a riddle correctly or die. Pericles, Prince of Tyre, tries his hand at the riddle. He is successful, but discovers that its answer reveals the incestuous relationship between father and daughter. Pericles doesn't reveal the truth, and Antiochus gives him forty days before his death sentence. But Pericles is sure Antiochus will want him dead for knowing the truth, so he flees back to Tyre. Antiochus sends an assassin after him.

In Tyre, Pericles worries that Antiochus will take some form of revenge, whether a military attack or an underhanded assassination attempt. Filled with melancholy, he takes the advice of Helicanus, his councilor, to travel for a while until Antiochus is no longer after him. Pericles first goes to Tarsus, where king Cleon and his wife Dionyza bemoan the famine that has beset their nation. Pericles arrives with corn and saves them. But soon a letter from Helicanus calls Pericles back to Tyre, so he sets off.

On the way home Pericles is shipwrecked in a storm in Pentapolis. Some fishermen tell him about king Simonides's daughter, a lovely girl who will be married to whoever wins a jousting contest the following day. Pericles determines to enter the contest. Though his is the rustiest armor, Pericles wins the tournament, and dines with Simonides and his daughter Thaisa, both of whom are very impressed with him.

Meanwhile in Tyre, Helicanus reveals that Antiochus and his daughter have been burnt to death by fire from heaven, so Pericles can return. Other citizens want to crown Helicanus as king, but Helicanus insists they wait to see if Pericles returns.

In Pentapolis, Pericles hears of recent events and determines to go back to Tyre. On board a boat with his wife and Lychordia, a nurse, they come upon a great storm, during which Thaisa dies in childbirth. The shipmaster insists the body be thrown overboard, or the storm won't stop, and Pericles complies. Thaisa's body is put in a chest, which washes up in Ephesus, where it is brought to the attention of Cerimon, a generous doctor. He discovers that Thaisa is not dead, and revives her.

Pericles lands in Tarsus and hands over his child, Marina, to Cleon and Dionyza, since he thinks it won't survive the journey to Tyre. Then times passes; Pericles is king of Tyre, Thaisa becomes a priestess for Diana, and Marina grows up. But Dionyza is jealous of Marina, who takes all the attention away from her own daughter who is of similar age. Dionyza plots to have Leonine murder Marina, but at the last moment, pirates seize her, and take her to Myteline on Lesbos to sell her as a prostitute.

Sold to a brothel run by Pander and Bawd, Marina refuses to give up her honor, despite the many men who come wanting to buy her virginity. She manages to convince the men who come to the brothel that her honor is sacred, and they leave seeking virtue in their own lives. Soon she gets work in a reputable house, educating girls. Meanwhile, Pericles goes on a trip to Tarsus to reunite with his daughter, but Cleon and Dionyza tell him that she has died, and show him the monument they have ordered built in order to erase their complicity in the matter. Pericles is distraught, and sets to the seas again.

Pericles and his crew arrive in Myteline, and Lysimachus goes out to meet the ships. Helicanus explains that Pericles has not spoken in three months, and Lysimachus says he knows someone in his city who may be able to make him talk. Marina is brought to the ship, and she tells Pericles that her own sufferings must match his. He asks her about her birth, and she says her name is Marina. Startled, Pericles asks her to continue, and to his surprise finds that everything Marina says matches the story of his own lost Marina. They are reunited, but Pericles is exhausted, and in his sleep the goddess Diana tells him to go to her temple in Ephesus and tell of his experiences. When he wakes, he promises Marina to Lysimachus, and they set off for Ephesus.

In Ephesus, Thaisa is a priestess at the temple where Pericles tells his story. When she realizes Pericles is her lost husband, she faints, and Cerimon explains that she is Thaisa. The whole family is reunited, and overjoyed.

Gower returns to offer a conclusion, noting that we have seen evil punished (Antiochus and his daughter have died, and when the people of Tarsus discovered Cleon's evil, they revolted and killed him and his wife in a palace fire), but that we have met a variety of good people along the way, such as loyal Helicanus and charitable Cerimon. Pericles and his family have endured the vagaries of fortune, and through it all remained virtuous, so in the end they were rewarded with the joy of being reunited.