Sexing The Cherry unfolds in a non-linear narrative, and includes perspectives from multiple different characters. The novel also experiments with ideas of time, memory, and fantasy, sometimes leaving it unclear whether events "really" happened, or exist mainly within the imagination of characters. The primary plotline begins around 1630 in London, England. Dog Woman is a giant and somewhat grotesque woman who lives an isolated life until she finds an infant boy on the banks of the Thames River. She names the boy Jordan and lovingly raises him. Jordan begins to go on fantastical "voyages" in which he travels to mysterious and magical places; it is not clear to what extent these voyages are real and to what extent they occur only within his imagination. These experiences prompt Jordan to think deeply about the nature of time, memory, and love, while Dog Woman remains much more pragmatic and literal.
In 1640, when Jordan is around 10, his hobby of sailing small boats in the Thames attracts the attention of a man named John Tradescant, who works as a gardener employed by King Charles I. Tradescant has voyaged to many places around the world, and collected specimens of exotic plants. A few years later, around 1642, Tradescant asks Jordan to begin working as his apprentice; Jordan and Dog Woman move to Wimbledon, where Tradescant is designing beautiful gardens for Queen Henrietta Maria. By this time, England has become embroiled in a Civil War between Parliamentarians (who challenged the authority of King Charles) and Royalists (loyal to the king and existing systems of power). The Parliamentarians were also closely associated with the Puritan religious movement; Dog Woman has a history of conflict with the Puritans, as she disagrees with their severe and moralizing approach to religion.
In 1649, King Charles I is put on trial and executed. Dog Woman, Jordan, and Tradescant watch the trial and execution in London; afterwards, Tradescant announces that he is going to depart on another voyage. Jordan, now aged 19, decides to go with his mentor, and Dog Woman parts from him with great sadness. The narrative follows Dog Woman and Jordan as they live separate lives for the next 13 years. Dog Woman stays in London, growing increasingly unhappy with the rigid control of the Puritan forces, who are now in power. Dog Woman supports the Royalist cause by personally killing many Puritans, notably two men whom she catches in a brothel.
Meanwhile, Jordan sails with Tradescant around the world. Either over the course of the voyage, or within the space of his imagination, Jordan catches a glimpse of a beautiful woman and becomes obsessed with finding her. He eventually encounters 11 princesses who all live together; they explain that, as a group of 12 sisters, they used to sneak out to go dancing at night, but eventually a prince solved the mystery of how they were escaping. As a reward, the prince and his 11 brothers married the 12 princesses; however, the youngest princess, named Fortunata, escaped on the wedding day. Eventually the other princesses also ended up single again. Jordan is convinced that Fortunata is the elusive woman he is pursuing, and continues to look for her.
Jordan eventually finds Fortunata on an isolated island where she runs a dancing school. He spends an idyllic month with her, but eventually has to return to sea, and Fortunata is unwilling to go with him. Eventually, in 1661, Jordan returns to England. He brings back the first pineapple ever seen in England. Dog Woman is very happy to see him again; by now, the monarchy has been restored in England and King Charles II is on the throne. Jordan is offered many riches and honors, but prefers to live a quiet life. He seems to still be pining for Fortunata.
Jordan and Dog Woman live together in London for some years; they endure a terrible outbreak of plague in 1665. After the plague, Dog Woman is unsettled and believes London should be destroyed; she is relieved and happy when a severe fire breaks out in 1666. By this time, Jordan and Dog Woman have already been planning to leave London.
A secondary narrative unfolds in 20th-century England; a young man named Nicholas Jordan grows up fascinated by boats, and eventually joins the navy. He hears about a woman who is an environmental activist, protesting corporations who are polluting water sources. Intrigued, Nicholas goes to meet her, and she suggests that the two of them set fire to a nearby factory that is dumping toxic chemicals into waterways. The two storylines converge with the fire in the contemporary plot line mirroring the fire of 1666. At the end of the novel, Jordan and Dog Woman sail away from London together; Jordan knows he will never return to England, and feels a sense of loss, but also hope for the future.
