Villette begins with its protagonist and unreliable narrator, Lucy Snowe, aged 14, staying at the home of her godmother Mrs. Bretton in "the clean and ancient town of Bretton", in England. Also in residence are Mrs. Bretton's teenaged son, John Graham Bretton (whom the family calls Graham), and a young visitor, Paulina Home (who is called Polly), who is aged 6. Polly's mother, who neglected her daughter, has recently died and her father is recommended by doctors to travel to improve his spirits. Polly is invited by Mrs. Bretton to stay. Polly is a serious little girl, who is described as unlike normal children.
Polly soon develops a deep devotion to Graham, who showers her with attention. But Polly's visit is cut short when her father arrives to summon her to live with him abroad.
For reasons that are not stated, Lucy leaves Mrs. Bretton's home a few weeks after Polly's departure. Some years pass, during which an unspecified family tragedy leaves Lucy without family, home, or means. After some initial hesitation, she is hired as a caregiver by Miss Marchmont, a rheumatic crippled woman. Lucy is soon accustomed to her work and has begun to feel content with her quiet, frugal lifestyle.
The night of a dramatic storm, Miss Marchmont regains all her energy and feels young again. She shares with Lucy her sad love story of 30 years ago, and concludes that she should treat Lucy better and be a better person. She believes that death will reunite her with her dead lover. The next morning, Lucy finds Miss Marchmont died in the night.
Lucy then leaves the English countryside and goes to London. At the age of 23, she boards a ship for Labassecour despite knowing very little French. On the ship, she meets Ginevra Fanshawe, who tells Lucy that the directress of her boarding school for girls (based upon the Hégers' Brussels pensionnat) she is attending, Madame Beck, needs a bonne for her children. She travels to the city of Villette in Labassecour where Madame Beck's school is located. After a time, she is hired to teach English at the school, in addition to having to mind Madame Beck's three children. She thrives despite Madame Beck's constant spying on the staff and students.
"Dr. John," a handsome English doctor, frequently visits the school at the behest of Madame Beck, and deepens his affection for the coquette Ginevra Fanshawe. In one of Villette's famous plot twists, "Dr. John" is later revealed to be John Graham Bretton, a fact that Lucy has known since he once asked her why she was staring at him, but has deliberately concealed from the reader.
During the school holidays, all the teachers and pupils have either gone to travel abroad or gone back to their families. The school is completely empty except for a disabled child whom Lucy is supposed to take care of. After the disabled child is fetched away, Lucy is extremely lonely and becomes both mentally and physically ill. She goes to a Catholic church (despite being a Protestant) to confess to a priest. On the way back to the school, she collapses due to fever and mental exhaustion. Dr. John brings her to his home, which he shares with his mother, Mrs. Bretton.
Graham recognises Lucy only after she is brought to Mrs. Bretton's home. After Dr. John (i.e., Graham) discovers Ginevra's true character while at the theatre, he turns his attention to Lucy, and they become close friends. She values this friendship highly despite her usual emotional reserve. Lucy soon develops feelings for Dr. John and treasures the letters he sends her once she returns to the pensionnat.
Lucy and Graham meet Polly (Paulina Home) again at the same theatre after a fire, in which Polly is injured. Polly's father has inherited the title "de Bassompierre" and is now a Count; thus her name is now Paulina Mary Home de Bassompierre. Polly and Graham soon discover that they knew each other in the past and slowly renew their friendship. They fall in love and eventually marry despite the initial reluctance of Polly's father.
Lucy becomes progressively closer to a colleague, the irascible, autocratic, and confrontational professeur, M. Paul Emanuel, a relative of Mme. Beck. Lucy gradually realises that his apparent antagonism is actually helping her to overcome her weaknesses and to grow. She and Paul eventually fall in love.
However, a group of conspiring antagonists, including Madame Beck, the priest Père Silas, and the relatives of M. Paul's long-dead fiancée, work to keep the two apart, on the grounds that a union between a Catholic and a Protestant is impossible. They finally succeed in forcing M. Paul's departure for Guadeloupe to oversee a plantation there. He nonetheless declares his love for Lucy before his departure and arranges for her to live independently as the headmistress of her own day school, which she later expands into a pensionnat.
During the course of the novel, Lucy has three encounters with the figure of a nun — which may be the ghost of a nun who was buried alive on the school's grounds as punishment for breaking her vow of chastity. In a highly symbolic scene near the end of the novel, she discovers the "nun's" habit in her bed and destroys it. She later finds out that it was a disguise worn by Ginevra's amour, Alfred de Hamal, placed in Lucy's bed as a prank. The episodes with the nun no doubt contributed substantially to the novel's reputation as a gothic novel. Ginevra keeps in contact with Lucy through letters that show the young coquette has not changed and expects to live off of her uncle's (Basompierre's) good graces.
Villette's final pages are ambiguous. Although Lucy says that she wants to leave the reader free to imagine a happy ending, she hints strongly that M. Paul's ship was destroyed by a storm during his return journey from the West Indies. She says that, "M. Emanuel was away three years. Reader, they were the three happiest years of my life." This passage suggests that he was drowned by the "destroying angel of tempest."
Brontë described the ambiguity of the ending as a "little puzzle" (quoted in Chapter XII of part 2 of Gaskell's Life).
