North and South takes place primarily in the city of Milton-Northern, a fictionalized version of Manchester, England, in the mid-19th century. The Hale family lives in the fictional suburb of "Crampton," a name that Gaskell uses to allude to overcrowded living and working conditions in much of the working-class metropolis during this time. Gaskell, a Unitarian minister's wife, lived in Manchester during its industrial boom and did relief work there, so she was very familiar with and concerned about the plight of the working poor there. The rise of industry had transformed life in Manchester so dramatically (the number of cotton mills peaked in the city when Gaskell wrote North and South in the 1850s) that it was nicknamed "Cottonopolis."
The novel's events revolve around the industrial revolution, which peaked in England from the late 18th century through the mid-19th. The industrial revolution was mainly fueled by the transition to new manufacturing methods (steam- and machine-driven and factory-based). The revolution's upsides included a rise in employment and overall boost in people's standard of living; however, workers, especially women and children, often had to contend with poor conditions and low wages. Bessy Higgins's fatal disease (unnamed in the novel but probably the lung disease byssinosis), contracted from poor working conditions, is an example. The novel also explores the emergence of trade unions and workers' strikes in response to such conditions, and the resulting antagonism between working and employer classes.
The novel's early and concluding chapters also take place in fictional Helstone (a village in the New Forest of southern England) and in London—specifically in the fashionable London neighborhood of Harley Street, where Margaret stays with her Aunt Shaw and cousin Edith. Both Harley Street and most of its inhabitants are portrayed as relatively frivolous compared to the people and places of the industrial North. Their lives revolve around clothes and dinner parties—and maintaining sharp lines between their comfortable world and the working class. Rural Helstone, in contrast, is idealized early in the novel as a harmonious community in tune with nature, unlike Milton. Yet at the end of the novel, Margaret recognizes that Helstone faces changes and challenges, too.