The events of the novel take place over several years, and are recounted through flashbacks and a narrative that appears to be recorded at the time that events occurred. This cannot be the case, though, as Offred has no access to recording material during the time remembered. The flashback episodes deal with the gradual emergence and coming to power of the Gilead regime.
The novel opens with Offred's memories of the Red Centre, where much of her memories reside. She strikes an elegiac tone to describe what existed before, and what she had. Her narrative is internal because of the amount of time she spends by herself as a Handmaid, and because she cannot talk to anyone openly.
In preparing to go out shopping, Offred describes the inhabitants of the house where she lives, what they do, and specifically her first meeting with the wife of the house, Serena Joy. We learn more about her later. Nick is mentioned as she leaves to meet Ofglen, who is her shopping partner.
When out shopping, Offred recounts the changes that have been made to the town where she has lived all her life, it seems. They see other Handmaids, including one who is pregnant, and also some Japanese tourists who provide a counter balance of near normality for the reader.
After shopping, Ofglen and Offred go to the Wall, where traitors' bodies are displayed as a warning to others. Once back, Offred slips off into thinking about the past and Moira; events of the novel are interspersed with memories of the past, and Moira plays a large part in Offred's thoughts. She also thinks about how her daughter was nearly kidnapped, and then her mother. These fragmented memories provide glimpses of the past that can be grafted together by the reader to understand what has happened.
Out, again, Ofglen subtly mentions the underground resistance movement called Mayday, but Offred does not respond and remains silent, as she does not understand the full implications of what has been said. When she goes back to the house, she thinks about how she recognised Serena Joy from the television before Gilead existed. Serena Joy used to be a singer, but then became a crusader for women staying at home. Luke and Offred used to laugh at her, though Offred saw the threat of what she symbolised. While going up to her room (which she acknowledges as her's for the first time), she sees that the Commander is there; his interest in her and breaking of the rules will develop later into a sort of relationship.
While having a routine gynaecological exam, Offred is approached by the doctor, who offers to impregnate her. She refuses it through silence.
From here, the next moment of significance is the Ceremony of mating, which is described in cold, clinical and cynical terms. This chapter is written in a detached style so that Offred can survive remembering it, and also because the actions are so clinical. However, she does acknowledge the difficulties that Serena Joy faces during the Ceremony, albeit ironically.
Afterwards, the Commander further breaks the rules through inviting Offred into his study. Nick is used as the go-between. In the Commander's study they play Scrabble together. The novelty of words and letters seems to be almost pornographic in its illicit nature. This is followed up with the Commander giving her fashion and beauty magazines to read. She feels like his mistress, which accentuates the loss of normal life for her.
Offred goes out shopping with Ofglen again, who finally broaches the subject of Mayday more explicitly. This symbol of hope seems to spur her on to think of the past more, and what happened when the Gileadean Republic was instigated. She remembers losing her bank account and her job, and the way that Luke did not seem to be bothered by her loss. She also thinks about Moira and her mother.
This hope continues when Serena Joy offers her information about her daughter in exchange for a baby. Serena suggests that the Commander might be infertile, and encourages Offred to sleep with Nick.
She does eventually receive a picture of what might be her daughter on the day of a Prayvaganza, where members of Gileadean society gather to celebrate arranged marriages. It is here that Offred hears that the baby born earlier on is dead (a 'shredder'), and this makes her think about how its mother often lost her mind whilst they were in the Red Centre.
Later on, in the evening, Offred's commander takes her out to a club, Jezebel's, where women are kept as whores. Moira is there, and tells Offred about what happened to her after she escaped from the Red Centre. However, Offred feels let down by Moira's attitude now, and thinks that she has been beaten and has given up. After Jezebel's, Offred tries to remember and tell the story of what passed between her and Nick. She cannot be satisfied with how she puts it, and tells it several times, looking for the truth in what has occurred.
This moment of sensual pleasure is followed by a salvaging the next day, where traitors are executed in public. A man who has apparently been convicted of raping a Handmaid is handed over to the Handmaids, and they are expected to tear him apart. Ofglen recognises him as a member of Mayday, and tried to make his suffering less.
Because of this, Ofglen later hangs herself, to protect her colleagues. Offred learns of this through the new Ofglen, who advises her to forget about Mayday and all that it stands for.
The story ends abruptly at night, with some Eyes appearing at the house, and asking for Offred. She thinks that she has been betrayed somehow, but Nick whispers that it is Mayday come to rescue her. This, however, is never made certain, and the reader is left in doubt as to what happens after the narrative ends.
That is not the end of the novel, though, as there is a parody of an academic symposium about the problems of authentification of this fictional story. There are suggestions in this final section that Gilead has ceased to exist, and that Caucasians are now an ethnic minority who are studied by what are now ethnic minorities. This part of the novel forces the reader to reappraise what they have read so far, and question the issues that have been raised. For example, Professor Pieixoto tries not to pass moral judgement on the Gileadean regime. This makes the reader think about atrocities in the past with the coldness of distance, and never with an emphasis on the individual.