The first section of I for Isobel, "The Birthday Present," finds protagonist Isobel Callaghan on vacation at a lakeside boarding house with her mother, her father, and her sister Margaret. Isobel's ninth birthday is approaching, but Isobel's mother has declared (as she does every year) that Isobel will not receive any presents: Isobel's birthday is in January, which is too close to Christmas for additional presents to be sensible, in her mother's opinion. Having accepted that her birthday might pass without incident, Isobel spends time reading The Adventures of Sherlock Holmes, an activity that impresses a few of the adults in the boarding house. Isobel, though, receives an unexpected birthday gift: a basket-shaped brooch with bells and flowers, which is given to her by a boarder named Mr Mansell. Isobel is impressed by the gift. However, her mother finds her and begins slapping and haranguing her; despite this violent disapproval, Isobel's mother does not take Isobel's brooch away.
In the opening of the novel's second section, "False Idols and a Fireball," Isobel sees a pink fireball streak past on her way home from school. Isobel's mother believes that her daughter is lying about this occurrence. In fact, dishonesty is one of the main traits that Isobel's mother attributes to her daughter, even though Isobel is not really a vicious or mean-spirited girl: she takes refuge in a private world of fictional characters, whom she contemplates in bed at night. Her mother, though, insistently demands for Isobel to show daughterly affection and accuses Isobel of losing a bracelet that belonged to Margaret, even though Isobel did no such thing.
The third section of the novel, "The Grace of God and the Hand-Me-Down," begins by explaining that Isobel felt infused with God's grace one day during mass. She tries to maintain her state of grace by overlooking her mother's scolding and disapproval. Isobel's mother, for her part, simply assumes that Isobel is sulking. Margaret has also experienced an important change in her life: she has been given a part in her school's play (a production of Shakespeare's Twelfth Night) and the performance will bring in boys from a nearby school for some of the parts. Isobel's mother disapproves of this development, and is further irritated when her prosperous sister-in-law Aunt Noelene visits the house. The two women have a tense exchange regarding the death of Isobel's father; before she leaves, Aunt Noelene gives Isobel and Margaret money and a bag of clothes as presents. Isobel finds that one of the articles of clothing meant for her is a splendid yellow dress. However, Isobel's mother rips this garment in anger, and Isobel lashes out, breaking her state of grace.
A time jump leads into the fourth and largest section of I for Isobel, "Glassware and Other Breakable Items." Isobel's mother has died, and Aunt Noelene and Aunt Yvonne (the other sister of Isobel's father) are attending to the funeral arrangements. Isobel does not feel much initial grief over her mother's passing; only when the household possessions begin to be dispersed does she begin to cry. From now on, Isobel will be living independently, with occasional help from Aunt Noelene. The young woman settles into a room in the boarding house run by Mrs Bowers, and begins her job translating German mail for a company that imports glassware: in this employment, she meets Mr Richard (whose attention and supervision are a source of anxiety and irritation) and Frank (a Communist who handles the inventory).
Isobel's intellectual life is transformed when she encounters a "special group" of young poets and literature students one day in a cafe. Under their direction, she is introduced to the works of poets such as W.H. Auden and novelists such as Fyodor Dostoevsky. This group includes Nick, who is still dealing with the obsessive attentions of a young woman named Diana, and Trevor, who attempts to begin a relationship with Isobel. Isobel's main problems during this phase include her worsening relationship with Mrs Bowers and her fears that the dark, brooding Diana might commit suicide. But death visits a very different character: Nick, who dies when he is hit by a car. Isobel brings the news to Diana (who is surprisingly unconcerned), offers assistance to Nick's mother, and then decides to leave Mrs Bowers, a move that Isobel finds refreshing.
The fifth and final section of I for Isobel is itself titled "I for Isobel"; it begins with Isobel waking up after a one-night stand with a young man named Michael. The two find that their morning interactions are strained and almost aggressive, so Isobel quickly shows herself out, but not before pilfering one of Michael's books. She goes shopping, buys materials for embroidery, and heads home to work on a design. Nonetheless, her thoughts are drawn back to the writings of saints and theologians described in Michael's book; she eventually sets out to revisit her hometown and to see its church through adult eyes. During this visit, Isobel encounters a neighbor from her youth, Mrs Adams, who invites Isobel in for tea. Isobel had at one point written a poem about Mrs Adams's cat, Smoke, and gotten it published in a newspaper; while Isobel had long assumed that Mrs Adams would be unhappy with this publicity, Mrs Adams reveals that she liked the poem as a memento of her cat. Isobel leaves, begins to cry, and acknowledges to herself that she is a writer. She goes home and begins to write a story based in part on her interactions with Michael. Witting's novel ends shortly after, with the image of Isobel at her desk in the import company, reflecting positively on all that has just transpired.
