In the mid-1980s near Boston, Massachusetts, a cabal of rightwing fundamentalists murders the U.S. President and members of Congress, disenfranchises women by impounding their credit cards and denying them jobs and education, and sets up Gilead, a repressively conservative state bent on annihilating homosexuals, abortionists, and religious sects other than their own, and resettling Jews, old women, and nonwhite people in radioactive territory, known as the Colonies. Because nuclear and biological warfare has polluted vast areas, the population suffers a sharp decline in viable births and a rise in birth defects. Consequently, infertile and aged females, as well as homosexuals, are dispatched as clean-up crews in the Colonies. Fertile women involved in illicit liaisons or second marriages are apprehended, indoctrinated, and parceled out to Commanders of the secret police as Handmaids. These reduniformed breeders live in seclusion and virtual slavery and are deprived of their real names and labeled with a patronym of the men who control their lives-as in "Ofcharles" and "Ofwarren." The purpose of these polygynous relationships is the perpetuation of the white race, which carries on warfare in outlying areas in a struggle for supremacy.
Offred, the second wife of Luke and mother of a five-year-old daughter, attempts to escape to Canada. She is apprehended and separated from her family. Her mother, a vocal feminist, disappears. Virtually alone and friendless, Offred is selected as a potential breeder and indoctrinated at the Rachel and Leah Re-Education Center. The Handmaids-in-training share pared-down barracks — like quarters in a gymnasium surrounded by fences topped by barbed wire. Reunited with her feisty, rebellious college pal Moira, Offred maintains spunk and individuality while pretending to follow the direction of sadistic armed matrons, particularly Aunt Lydia and Aunt Elizabeth.
After lights out, Moira, Offred, and other Handmaids offer surreptitious support, survival tips, and bits of information. Like conspirators, they observe the patrolling Aunts and seize unguarded moments for normal behavior, including gripe sessions, food stolen from the cafeteria, and brief touches of hands between cots. Janine, a compliant stooge, struggles so hard to adapt to the restrictive Handmaid lifestyle that she retreats into a blank stare, evidence of impending mental and emotional collapse. Because Moira pretends to suffer an attack of appendicitis, she is tortured by beatings with steel cables on her feet. Ultimately, she overpowers Aunt Elizabeth, strips her, and escapes in the Aunt's khaki uniform.
Offred leaves the Center and joins the robotic cadre of Gilead's Handmaids. After one failed attempt to conceive, she passes into the possession of a second official, Commander Fred, whose previous Handmaid hanged herself from the bedroom light fixture. Daily, Offred carries a basket to local markets to obtain fresh food, then returns to a boring incarceration in a cloistered room, relieved only by public prayer sessions, birthings, monthly medical exams, and executions. Once a month she mates with Commander Fred in a pseudo-religious ritual requiring Bible reading, followed by copulation with the Commander in the presence of his aging Wife, Serena Joy. A spiteful, unhappy former gospel singer, Serena at first disdains Offred, then grows so despondent at their mutual barrenness that she arranges for Offred to conduct a secret sexual liaison with Nick, the family chauffeur.
Unknown to Serena, the Commander has been summoning Offred to late-night visits to his den for companionship, games of Scrabble, kisses, and gifts of hand lotion, fashion magazines, and information about the outside world. Offred divulges a Latin phrase that her predecessor scratched on the wall. The Commander translates it for her. On one of her visits, the Commander presents her with borrowed finery — makeup, high heels, a sequined and feathered costume, and an evening cloak. Offred abandons her standard red outfit and, dressed in whorish frippery, accompanies him to Jezebel's, an illegal nightclub staffed by prostitutes and frequented by Gilead officials and Japanese and Arab businessmen. Offred locates Moira among the prostitutes and pumps her for information. Moira relates her failed attempt to escape Gilead and reports seeing a documentary film that contained a glimpse of Offred's mother, now an Unwoman at a radioactive Colony.
On a late summer day, Serena confronts Offred with the garish sequined garment and accuses her of treachery. As Offred contemplates her alternatives — escape, suicide, retreat to Nick's quarters, a plea for mercy from the Commander — a black police van arrives. Nick enters her room and hurries her into the custody of two operatives of the Eyes, whom he indicates are double agents for Mayday, the underground liberation group that Ofglen has hinted at. Against the Commander's objections, the two agents charge Offred with violating state secrets and hustle her into the waiting van. Her narrative ends with her ambiguous departure from the Commander's custody.
On June 25, 2195, over two centuries after the formation of Gilead's theocratic dictatorship, an academic consortium listens to a keynote speech delivered by Professor James Darcy Pieixoto, an archivist who gives evidence of Offred's experiences as narrated on thirty cassette tapes. The unnumbered segments do not establish the existence of a real historical figure, but shreds of data suggest that the voice on the tapes belongs to a single speaker who identifies a real Commander, possibly Frederick R. Waterford, who was eradicated during a state purge of liberals. Pieixoto's surmise is that Offred escaped Gilead on the Underground Femaleroad, connected with a Quaker way station in Bangor, Maine, and concealed her story on pre-recorded commercial tapes before departing to either Canada or England. Pieixoto assumes that Offred lived out her life in seclusion to spare her family from lethal reprisals.