Like the show's first season, The Handmaid's Tale novel follows Offred as she navigates her role as a handmaid to one of the powerful Commanders in charge of Gilead. As the novel progresses, she faces abuse from the Commander's wife and forms a more intimate bond with the Commander. By the end of the novel, Offred has learned of a secret resistance movement called Mayday, and has also begun a sexual relationship with Nick, the Commander's driver.

Offred begins to suspect that she's pregnant with Nick's child, and after discovering that, the Commander's wife learns about her relationship with the Commander. In the end, a group known as the Eyes, who watch over everything in Gilead, come to take Offred away. Nick tells her to trust him, but Offred is confused about whether Nick is a member of Mayday or is secretly working with the powers in Gilead. She gets in the van and it drives away.