After a staged attack that killed the President of the United States and most of Congress, a radical political group called the "Sons of Jacob" uses theonomic ideology to launch a revolution.[8] The United States Constitution is suspended, newspapers are censored, and what was formerly the United States of America is changed into a military dictatorship known as the Republic of Gilead. The new regime moves quickly to consolidate its power, overtaking all other religious groups, including Christian denominations.
The regime reorganizes society using a peculiar interpretation of some Old Testament ideas, and a new militarized, hierarchical model of social and religious fanaticism among its newly created social classes. One of the most significant changes is the limitation of women's rights. Women become the lowest-ranking class and are not allowed to own money or property, or to read and write. Most significantly, women are deprived of control over their own reproductive functions. Though the regime controls most of the country, there are various rebel groups that are still active.
The story is told in first-person narration by a woman named Offred. In this era of environmental pollution and radiation, she is one of the few remaining fertile women. Therefore, she is forcibly assigned to produce children for the "Commanders", the ruling class of men, and is known as a "Handmaid" based on the biblical story of Rachel and her handmaid Bilhah. She undergoes training to become a handmaid along with other women of her standing at the Rachel and Leah Centre.
Apart from Handmaids, women are classed socially and follow a strict dress code, ranked highest to lowest: the Commanders' Wives in sky blue, the Handmaids in red with large white bonnets to be easily seen, the Aunts (who train and indoctrinate the Handmaids) in brown, the Marthas (cooks and maids, possibly sterile women past child-bearing years) in green, Econowives (the wives of lower-ranking men who handle everything in the domestic sphere) in blue, red and green stripes, and widows in black.
Offred details her life starting with her third assignment as a Handmaid to a Commander. Interspersed with her narratives of her present-day experiences are flashbacks of her life before and during the beginning of the revolution, including her failed attempt to escape to Canada with her husband and child, her indoctrination into life as a Handmaid by the Aunts, and the escape of her friend Moira from the indoctrination facility. At her new home, she is treated poorly by the Commander's wife, Serena Joy, a former Christian media personality who supported women's domesticity and subordinate role well before Gilead was established.
To Offred's surprise, the Commander requests to see her outside of the "Ceremony", which is a ritualised rape conducted during the Handmaids’ likely fertile period each month (conducted in the presence of the wives), intended to result in conception. The Commander's request to see Offred in the library is an illegal activity in Gilead, but they meet nevertheless. They mostly play Scrabble and Offred is allowed to ask favours of him, either in terms of information or material items. The Commander asks Offred to kiss him "as if she meant it" and tells her about his strained relationship with his wife. Finally, he gives her lingerie and takes her to a covert, government-run brothel called Jezebel's. Offred unexpectedly encounters Moira there, with Moira's will broken, and learns from Moira that those who are found breaking the law are sent to the Colonies to clean up toxic waste or are allowed to work at Jezebel's as punishment.
In the days between her visits to the Commander, Offred also learns from her shopping partner, a woman called Ofglen, of the Mayday resistance, an underground network working to overthrow the Republic of Gilead. Not knowing of Offred's criminal acts with her husband, Serena begins to suspect that the Commander is infertile, and arranges for Offred to have a covert sexual encounter with Nick, the Commander's personal servant. Serena offers Offred information about her daughter in exchange. She later brings her a photograph of Offred's daughter which leaves Offred feeling dejected because she senses she has been erased from her daughter's life.
Nick had earlier tried to talk to Offred and had shown interest in her. After their initial sexual encounter, Offred and Nick begin to meet on their own initiative as well, with Offred discovering that she enjoys these intimate moments despite memories of her husband, and shares potentially dangerous information about her past with him. Offred tells Nick that she thinks she is pregnant.
Offred hears from a new walking partner that Ofglen has disappeared (reported as a suicide). Serena finds evidence of the relationship between Offred and the Commander, which results in Offred contemplating suicide. Shortly afterward, men arrive at the house wearing the uniform of the secret police, the Eyes of God, known informally as "the Eyes", to take her away. As she is led to a waiting van, Nick tells her to trust him and go with the men. It is unclear whether the men are actually Eyes or members of the Mayday resistance.
Offred is still unsure if Nick is a member of Mayday or an Eye posing as one, and does not know if leaving will result in her escape or her capture. Ultimately, she enters the van with her future uncertain while Commander Fred and Serena are left bereft in the house, each thinking of repercussions of Offred's capture on their lives.
The novel concludes with a metafictional epilogue, described as a partial transcript of an international historical association conference taking place in the year 2195. The keynote speaker explains that Offred's account of the events of the novel was recorded onto cassette tapes later found and transcribed by historians studying what is then called "the Gilead Period".
