The story of Nicolas Nickleby begins with the death of Nicolas's father. Without the family's breadwinner, they are at a loss for money and Nicholas decides to leave home in search of work. In this instance, death is a plot device that serves to create the main stakes of the story.
Nicholas seeks employment at a boarding school run by Wackford Squeers through an arrangement with his uncle, Ralph, who promises to care for his mother and sister while Nicholas works. He quickly learns that Squeers takes such deplorable care of his students that they are beaten and starved to death. While Nicholas wants to protect his mother and sister, the deaths of innocent children are too much for him to bear, and so again, death intervenes to force him to fight back against Squeers and ultimately abandon his post, taking with him an unpaid laborer at the school, named Smike.
Nicholas's sister, Kate, has been used by Ralph as a plot to extort money from some wealthy men he knows, Lord Verisopht and Sir Mulberry Hawk. The two men treat Kate horribly, and she hates her time with them. They leer over her, and she is afraid she will be forced to marry one of the men should the arrangement continue. After many months away working to clear his name and find financial footing, Nicholas is able to return and save Kate from her destiny.
After many months of hard work to establish a safe life for him, his family, and Smike, Nicholas finds himself living in a cottage and working for the Cheeryble brothers, who have taken a liking to the family. Once they see that Nicholas and Smike are safe and happy, Nicholas's uncle and Wackford Squeers conspire to kidnap the boy. They ultimately fail, but Smike dies only a few months later from tuberculosis.
While working for the Cheeryble brothers, Nicholas meets Madeline Bray and falls in love with her. Madeline's father, Walter, owes money to Ralph, and an elderly man, Arthur Gride, offers to pay that debt in exchange for Madeline's hand in marriage. Walter agrees but dies only an hour before the ceremony was set to take place. Again, death saves Nicholas's story.
In the wake of the plot to steal the Bray fortune, Ralph learns that Smike, the young boy he tried to kidnap, is his son. A man who Ralph had wronged years ago had lied and told him his son had died at birth when instead he was sent to the very orphan school where Squeers abused children. Ralph is beside himself with grief and hangs himself. As the antagonist of the story and Nicholas's life, Ralph's death resolves an ongoing problem for Nicholas and furthers the narrative.
Finally, the story ends with happiness for both Nicholas and his sister, Kate, as they are allowed to marry the people they love and have their happy ever after. Death comes again to fight for justice by taking the lives of Arthur Gride, Lord Verisopht, and Sir Mulberry Hawk.