A prologue introduces the Nicklebys, country gentry who enjoy a comfortable life in the Devon countryside until the father Mr Nickleby (Andrew Havill) dies and leaves his family with no source of income (he had speculated his wealth on the stock market and lost heavily, prior to his death). Nineteen-year-old Nicholas (Charlie Hunnam), his mother Catherine (Stella Gonet), and his younger sister, Kate (Romola Garai), venture to London to seek help from their wealthy, cold-heart uncle Ralph (Christopher Plummer), a speculative investor who arranges for Nicholas to be hired as a tutor at Dotheboys Hall in Yorkshire and finds Kate work as a seamstress.Nicholas is horrified to discover his employers, the sadistic Mr Wackford Squeers (Jim Broadbent) and Mrs. Squeers (Juliet Stevenson), run their boarding school like a prison and physically, verbally, and emotionally abuse their young charges on a regular basis. Wackford won't allow the boys any correspondence with the outside world. He keeps all the money and gifts sent to the boys by their well-wishers and gives the gifts to his own son & daughter Fanny (Heather Goldenhersh). Meanwhile the young boys sleep in cattle shed, without a proper bed or blankets. They are fed brimstone for breakfast. Smike is a crippled servant of the school, who is treated worse than the others.Fanny takes a liking to Nicholas. But Nicholas rebuffs her advances. The Squeers take their frustration out on Smike, by increasing his workload to inhumane levels. Smike and Nicholas become friends and Nicholas really cares for Smike.Smike manages to run away by himself, but the Squeers launch a manhunt and bring him back. Wackford flogs Smike mercilessly as punishment.Nicholas eventually rebels (& flogs Wackford with his own cane) and escapes, taking with him the crippled young servant boy Smike (Jamie Bell). As they journey to London, they stumble upon a theatrical troupe owned and operated by Mr. Vincent Crummles (Nathan Lane) and Mrs Crummles (Barry Humphries).They cast them in a production of Romeo and Juliet. Mr. Folair (Alan Cumming) is a fellow actor at the troupe and warns Nicholas about the production quality of the troupe, which he considers abysmal. Despite a successful first night and the couple's invitation to stay, Nicholas is determined to continue their journey to London after hearing that Kate is in trouble.Meanwhile the Squeers have written to Ralph accusing Nicholas of attacking Wackford & stealing Mrs Squeers ring. They demand compensation of 28.10 pounds. Ralph feels cheated by Nicholas, as he has received news that Nicholas is on his way to Liverpool, perhaps to catch a ship and escape the country. This encourages Ralph to use Kate for furthering his own business purposes.Nicholas discovers his sister has been subjected to humiliating sexual harassment from the lecherous Sir Mulberry Hawk (Edward Fox), a client of their uncle, who has encouraged the man to seduce his niece (Ralph takes Kate to the theatre, where Hawk was already waiting. Hawk proceeds to grope at Kate at the end of the act, when everybody has left, despite her protests) in the hope that she will succumb and thus cement Hawk's business relationship with him. Newman Noggs (Tom Courtenay), Ralph Nickleby's butler is sympathetic to Kate and detests Ralph's treatment of Kate. He is the one who sends word to Nicholas.Nicholas confronts Sir Mulberry and his uncle, renouncing the latter. Lord Verisopht (Nicholas Rowe) is witness to Ralph's treatment of Nicholas and Kate and decides not to invest his money with Ralph.Nicholas is reunited with his family, who welcome Smike as one of their own, and finds clerical employment with the kindly Cheeryble brothers Charles (Timothy Spall) & Ned (Gerard Horan), who offer him more than double his previous salary (new salary of 120 pounds per year). While thus employed, Nicholas makes the acquaintance of Madeline Bray (Anne Hathaway), an artist who financially supports both herself and her tyrannical father Mr. Nigel Bray (David Bradley), after he gambled away his fortune and that of his late wife. Charles was in love with Madeline's mother, but she made the choice to go with Nigel. Charles feels obligated to take care of Madeline. Charles supports Madeline by buying her paintings via Nicholas. This way Madeline falls in love of Nicholas.Nicholas' determination to defend his sister's honor leads his uncle to vow he will destroy the young man. What ensues is a series of adventures in which the upstanding Nicholas manages to survive the schemes of his evil uncle, including an attempt to return Smike to Squeers by kidnapping him (Ralph calls Wackford and offers him 50 pounds, to lodge a police complaint against Nicholas for kidnapping Smike, who is under the legal guardianship of the Squeers. Nicholas works with John Browdie (Kevin McKidd), an employee of Wackford, but sympathetic to Nicholas and Smike to rescue Smike) and an effort to abort Nicholas' growing relationship with Madeline by promising her father he will excuse his debts if the girl weds Hawk.Ralph's designs on Madeline are thwarted when her father dies unexpectedly. Unfortunately, Smike falls ill and soon dies. Soon after, a sinister secret Ralph has harbored for years surfaces, and it is revealed Smike was Ralph's son, whom he had thought dead. Ralph had married in secret and his wife's father would have cut her out of his will, if he had known that she had married against his consent. The wife got pregnant and since the marriage was a secret, the boy had to be kept secret too. So, Ralph kept the boy hidden in the attic, where he got crippled. The doctors asked him to send away from London and Ralph gave the task to one of his servants. The servant took pity on the boy and reported to Ralph that he died, but he had sent the boy to the Squeer's school instead. At first the servant paid for him, but then couldn't afford the payments, due to which Smike became a servant at the school himself.Realizing that his son had died, the best friend of his most hated enemy Nicholas (and that he lost 10000 pounds in his investments), Ralph hangs himself.Kate marries the Cheeryble brothers' nephew Frank (William Ash), while Nicholas marries Madeline and settles with her in Devon at his father's house and grounds, where Smike is buried.