Vanity Fair follows the lives of Becky Sharp and Amelia Sedley amid their friends and families during and after the Napoleonic Wars. The two women are ostensibly friends, who are always in opposition to one another: when Amelia falls into a crisis, Becky is moving in the highest circles of society. When Amelia comes into luck, Becky's fortunes plummet. Throughout the novel, Amelia yearns for love, while Becky fights her way up the social ladder.

Vanity Fair reflects Thackeray's interest in deconstructing his era's conventions regarding literary heroism. The characters are all flawed to a greater or lesser degree; even the most sympathetic have weaknesses. The human weaknesses Thackeray illustrates are mostly to do with greed, idleness, and snobbery, and the scheming, deceit and hypocrisy which mask them. Vanity Fair is sometimes considered the "principal founder" of the Victorian domestic novel.