Sir Leicester Dedlock and Honoria, Lady Dedlock (his junior by more than 20 years) live at his estate of Chesney Wold. Lady Dedlock is a beautiful, haughty woman who is very admired in the social world because of her good looks, fine clothes and regal bearing. Her comings and goings are considered the choicest gossip among the "fashionable intelligence." Unknown to Sir Leicester, Lady Dedlock had a lover, Captain Hawdon, before she married Sir Leicester – and had a child by him, Esther Summerson. Lady Dedlock, believing her daughter is dead, has chosen to live out her days 'bored to death' as a fashionable lady of the world.
Esther is raised by Miss Barbary, Lady Dedlock's spartan sister, who instils a sense of worthlessness in her that Esther will battle throughout the novel. She holds a sort of depressed vigil on Esther's birthday each year, explaining that Esther's birth is no cause for celebration and that she was "her mother's shame." Esther doesn't know that Miss Barbary is her aunt, thinking of her only as her godmother. When Miss Barbary dies, the Chancery lawyer Conversation Kenge takes charge of Esther's future on the instruction of his client, John Jarndyce. Jarndyce becomes Esther's guardian, and after attending school in Reading for six years, Esther moves in with him at Bleak House, along with his wards, Richard Carstone and Ada Clare. Esther is to be Ada's companion.
Esther soon befriends both Ada and Richard, who are cousins. They are beneficiaries in one of the wills at issue in Jarndyce and Jarndyce; their guardian is a beneficiary under another will, and in some undefined way the two wills conflict. No one realizes that Esther (as Lady Dedlock's biological daughter) is also connected to Jarndyce and Jarndyce. Richard and Ada soon fall in love, but though Mr. Jarndyce doesn't oppose the match, he stipulates that Richard (who is inconstant) must first choose a profession. Richard first tries the medical profession, and Esther first meets the newly qualified Dr. Allan Woodcourt at the house of Richard's prospective tutor, Mr. Baynham Badger. When Richard mentions the prospect of gaining from the resolution of Jarndyce and Jarndyce, John Jarndyce beseeches him never to put faith in what he calls "the family curse".
Meanwhile, Lady Dedlock is also a beneficiary under one of the wills in Jarndyce and Jarndyce. Early in the book, while listening to her solicitor, the close-mouthed but shrewd Mr. Tulkinghorn, read an affidavit aloud, she recognises the handwriting on the copy. The sight affects her so much that she almost faints, which Tulkinghorn notes and thinks should be investigated. He traces the copyist who turns out to be a pauper known only as "Nemo" who has recently died. The only person to identify him is a street-sweeper, a poor homeless boy named Jo.
Lady Dedlock also investigates the matter disguised as her French maid, Mademoiselle Hortense. She pays Jo to take her to Nemo's grave. Meanwhile, Tulkinghorn is convinced that Lady Dedlock's secret might threaten the interests of his client, Sir Leicester Dedlock, and watches her constantly, even enlisting the help of the maid, who detests her. He also enlists Inspector Bucket to run Jo out of town, so that there are no loose-ends that might connect Nemo to the Dedlocks.
Esther meets her mother at church and talks with her later at Chesney Wold – though, at first, neither woman recognizes the tie that binds them. Later, Lady Dedlock realises that her abandoned child is not dead and is, in fact, Esther. She waits to confront Esther with this knowledge until Esther survives an unidentified disease (possibly smallpox, as it permanently disfigures her), which she got from the homeless boy Jo after Esther and her maid Charley attempted to nurse him back to health. Though they are happy to be reunited, Lady Dedlock tells Esther that they must never acknowledge their connection again.
Esther recovers, but her beauty is supposedly ruined. She finds that Richard, having failed at several professions, has ignored his guardian and is wasting his resources in pushing Jarndyce and Jarndyce to conclusion (in his and Ada's favour). Further, he has broken with his guardian, under the influence of his lawyer, the odious and crafty Mr. Vholes. In the process of becoming an active litigant, Richard has lost all his money and is breaking his health. In further defiance of John Jarndyce, he and Ada have secretly married, and Ada is carrying Richard's child. Esther experiences her own romance when Dr. Woodcourt returns to England, having survived a shipwreck, and continues to seek her company despite her disfigurement. Unfortunately, Esther has already agreed to marry her guardian, John Jarndyce.
Hortense and Tulkinghorn discover Lady Dedlock's past. After a quiet but desperate confrontation with the lawyer, Lady Dedlock flees her home, leaving a note apologising for her conduct. Tulkinghorn dismisses Hortense, no longer any use to him. Feeling abandoned and betrayed by Lady Dedlock and Tulkinghorn, Hortense kills Tulkinghorn and seeks to frame Lady Dedlock for his murder. Sir Leicester discovers his lawyer's death and his wife's flight, and he suffers a catastrophic stroke but manages to communicate that he forgives his wife and wants her to return to him.
Inspector Bucket, who up to now has investigated several matters on the periphery of Jarndyce and Jarndyce, accepts the commission of the stricken Sir Leicester to find Lady Dedlock. He suspects Lady Dedlock, even after he arrests George Rouncewell (the only other person known to be with Tulkinghorn on the night of the murder and to have quarrelled with him repeatedly). Bucket asks Esther to help search for Lady Dedlock. By this point, Bucket has cleared Lady Dedlock by discovering Hortense's guilt, but Lady Dedlock has no way to know this and wanders the country in cold weather before dying at the cemetery of her former lover Captain Hawdon (Nemo). Esther and Bucket find her there.
Developments in Jarndyce and Jarndyce seem to take a turn for the better when a later will is found which revokes all previous wills and leaves the bulk of the estate to Richard and Ada. Meanwhile, John Jarndyce cancels his engagement to Esther, who becomes engaged to Dr. Woodcourt. They go to Chancery to find Richard and to discover what news there might be of the lawsuit's resolution. To their horror, they learn that the new will has no chance to resolve Jarndyce and Jarndyce, for the costs of litigation have consumed the estate. Richard collapses, and Dr Woodcourt determines that he is in the last stages of tuberculosis. Richard apologises to John Jarndyce and dies, leaving Ada alone with their child, a boy she names Richard. Jarndyce takes in Ada and the child. Esther and Woodcourt marry and live in a Yorkshire house which Jarndyce gives to them. In time, they have two daughters.
Many of this intricate novel's subplots deal with the minor characters and their diverse ties to the main plot. One of these subplots is the hard life and happy though difficult marriage of Caddy Jellyby and Prince Turveydrop. Another focuses on George Rouncewell's rediscovery of his family at Chesney Wold and his reunion with his mother and brother.