Though she is called Offred in the story, the narrator's true name remains unknown. In the pre-Gilead United States, she is a college-educated woman with a job, a husband, and a daughter. When the Republic of Gilead seizes control, she loses everything, including her freedom. She is sent to a reeducation center with other fertile women, where she is taught about being a Handmaid—her new prescribed role in society. As a Handmaid, she must live with wealthy couples to provide them with children. Offred narrates the story of her life as a Handmaid and her struggle to survive and hold on to a sense of self despite her current circumstances and her tragic losses, which are revealed through a series of flashbacks and dreams.
As one of the men who leads the government coup and designs the social structure of the new Gilead, the Commander is a powerful, wealthy man. He epitomizes the oppressive system that has taken away everything of value to Offred and consigned her to a life of sexual slavery. He seems to have some regret that Gilead's rules cause Offred and other women such suffering, but he believes in the necessity of these rules to create a better future. However, he admits that this future might be better for only some people. While he must obey the rules to some extent, he also has greater ability to subvert the rules. He has more privacy than most, so he can pursue secret affairs, visit brothels, and employ servants who will not betray him.
A former religious television personality and anti-feminist speaker, Serena Joy was a darling of the religious fundamentalist movement before the establishment of the new Gilead. However, she, like the other women, loses both her career and her freedom when the fundamentalist vision of society becomes a reality. In the Commander's household, her freedom is severely restricted, although she is allowed some control over the servants, over the garden, and over Offred. As a childless woman, Serena Joy must tolerate the presence of a Handmaid, although she makes it clear that the arrangement is distasteful. In Gilead, the ability to have a child is one of the only things valued about women, so Serena Joy's value to society hinges on Offred's ability to give birth to a child on her behalf. This situation makes the relationship between Serena Joy and Offred strained, as the women need each other for survival but resent this need.
As a Guard—a low-level servant—in the Commander's household, Nick takes care of the Commander's car, acts as the chauffeur, and conveys messages to Offred when the Commander wants to see her secretly. He eschews social norms by making eye contact and speaking informally with women. He is an enigmatic figure—willing to conspire with Serena Joy to impregnate Offred but then carrying on an illicit affair with Offred behind both Serena Joy's and the Commander's backs. Offred has early suspicions that he is an Eye (a spy for the government), but later in the story, there are suggestions that he is a member of Mayday, the resistance.
Like Offred, Moira is assigned to a reeducation center to become a Handmaid. She escapes by threatening to kill one of the Aunts (the women in charge), but she is recaptured and tortured before she can cross the border out of Gilead. Now considered ill-suited to be a Handmaid, she is reassigned to the brothel Jezebel's, where she provides sex for high-ranking and foreign men. Moira is a dominant figure in Offred's imagination and memory, and Offred is discouraged when she learns that Moira has become a prostitute.