North and South is set in a fictional town called Milton and located north of England. The heroine Margaret Hale arrives here, having suffered a series of unfortunate events. Her father, a wealthy churchman who lives in the idyllic English countryside suddenly finds himself losing the faith that has sustained him all these years. He leaves the church and moves his family to this preindustrial, ugly and uninspiring city, where poverty, crime and hopelessness dominate. Margaret soon encounters the handsome, but materialistic, cotton mill owner and tycoon, John Thornton. Their values and philosophies are poles apart, leading to an inevitable clash, which forms the basis of the title of the novel, North and South.

The book traces the advent of the Industrial Revolution in England, the pathetic condition of workers and the callous, greedy attitude of the mill owners who formed the bedrock of the new rich in the country. She also wrote several very popular ghost stories which were regularly published by Dickens in his magazine, Household Words. However, Mrs. Gaskell's works, though immensely popular in her lifetime, soon faded into obscurity.

Today, her works are known chiefly through television adaptations of her novels like Cranford and North and South. Her enduring themes of tradition verses modernity, feminism, the changing nature of relationships and the falsity of first impressions all resonate with the interests of readers today.