As Vanity Fair opens, an unnamed narrator introduces the audience to the two main characters: Becky Sharp, the protagonist, who is a poor but clever young woman, and her friend, Amelia Sedley, the sweet, naive daughter of a middle-class family. Becky and Amelia have finished their schooling and are going to Amelia’s home in London, after which Becky will take up her job as a governess in the country. Becky meets Amelia’s fiancé George, his army friend William Dobbin, and Amelia’s brother Jos, who is on the brink of proposing to Becky until George scares him off. Becky continues to her job at the estate belonging to Sir Pitt Crawley, an ill-mannered but wealthy aristocrat. She quickly charms everyone she meets and wins over Sir Pitt, his second son Rawdon, and his wealthy half-sister, Miss Crawley. When Becky goes to London to attend to an ailing Miss Crawley, Sir Pitt makes a surprise visit to propose. However, Becky must refuse because she is already married—to Rawdon. Miss Crawley learns about the marriage of Rawdon and Becky—of her nephew to a governess—and tells Rawdon she will disinherit him.

Meanwhile, Amelia’s father has gone bankrupt, leading George’s father, Mr. Osborne, to break the engagement. Dobbin, who has loved Amelia since they first met, buys back Amelia’s piano from an auction, hoping to make her happy. Amelia thinks the piano is a gift from George. Dobbin realizes Amelia will be miserable without George, so he helps them elope, which leads George to be disowned. Amid the marriages and attempts to reconcile, war breaks out, and Dobbin, George, and Rawdon are all sent to Belgium. In the weeks before the regiments march into battle, Becky captivates George, and he passes her a secret note. Even the good-natured Amelia sees the flirtation, and she accuses Becky of attempting to steal her husband. George dies in battle, and Amelia returns to England with her baby, Georgy, where she remains devoted to her dead husband. Dobbin secretly supports Amelia, but he relocates to India when he sees that he has no chance of winning her affection.

Becky and Rawdon live in Paris until they learn that Miss Crawley is dying. They return to London with their son Rawdy. Although Miss Crawley doesn’t leave Rawdon her fortune, they still use her name to procure a home and everything they need on credit. Becky hosts gatherings for wealthy people and becomes a close friend of the illustrious Lord Steyne. She also becomes close with her brother-in-law, Pitt Crawley, who has inherited his father’s estate and title. Pitt’s wife, Lady Jane, sees through Becky’s manipulations. Becky spends her time socializing and social climbing, ignoring her husband and son. She also borrows money from Lord Steyne but lies to him about using it to pay off the household’s debt. Rawdon gets arrested for debt, but when Becky fails to bail him out of prison, he turns to Lady Jane. Upon Rawdon’s unexpected return home, he finds Becky and Lord Steyne in an intimate dinner. Assuming they are having an affair, Rawdon assaults Lord Steyne. Though the two men seem destined to duel, Lord Steyne gets Rawdon a job on a distant island, and Rawdon leaves his son in the care of Pitt and Lady Jane. Becky’s reputation is too tarnished to remain in London, and she leaves England.

Throughout this period, Amelia is living in poverty with her parents and son. She focuses on Georgy and spoils him. When the family faces financial hardship, however, Amelia makes the difficult decision to allow Georgy to be raised by his grandfather in return for an allowance. Eventually, the Sedleys die, and Jos and Dobbin return to England. Dobbin has been talking with Mr. Osborne about Amelia, and when the older man dies, he provides for Georgy and Amelia.

The Sedleys and Dobbin go to the Continent, where Amelia and Dobbin enjoy spending time together and are truly happy. In Germany, however, Jos meets Becky at a gambling hall. She has been moving around the Continent, never staying too long in one place because her reputation catches up with her. Since Jos and Amelia don’t know about her London exploits, they take pity on her and invite her to live with them despite Dobbin’s warnings. As Dobbin tries to make Amelia listen to him, he confesses his love for her. Amelia remains true to her husband’s memory, finally making Dobbin realize he has wasted his life pining for a woman who isn’t worthy. Dobbin goes back to England. Even Becky becomes frustrated with Amelia’s stubborn clinging to George, so she shows Amelia the note George slipped her on the night before the men marched off to battle. He had asked Becky to run away with him. A short time later, responding to a letter from Amelia, Dobbin returns. He and Amelia marry and settle in England, near Queen’s Crawley, with Georgy and their daughter.

Eventually, Rawdon and Pitt die, and Rawdy inherits the Crawley estate. Rawdy and Georgy become great friends and attend college together. Becky travels throughout the Continent with Jos. Then Amelia and Dobbin learn that Jos has taken out a large life insurance policy, and they worry that he is in debt. Dobbin goes to Brussels to ensure that Jos’s financial affairs are in order. The two men meet in Jos’s hotel room. Jos is unwell and afraid of Becky. Dobbin begs him to break off the relationship. While Jos claims he wants to do so, he says if Becky knew, she might kill him. Dobbin leaves and never sees Jos again. Jos dies three months later, leaving half of his assets to Becky. The insurance company suspects foul play but ends up paying out on the policy. Becky returns to England and lives the life of a genteel lady interested in charitable works. Amelia and her family encounter Becky one day at a charity event, and they scurry away without saying a word.