It was Brontë's second published novel after Jane Eyre (originally published under Brontë's pseudonym Currer Bell). The novel is set in Yorkshire in the period 1811–12, during the industrial depression resulting from the Napoleonic Wars and the War of 1812. The novel is set against a backdrop of the Luddite uprisings in the Yorkshire textile industry.

While Brontë was writing Shirley, three of her siblings died. Her brother Branwell died in September 1848, and her sister Emily fell ill and died in December. Brontë resumed writing, but then her only remaining sibling, her sister Anne, became ill and died in May 1849.

It is believed that the character of Caroline Helstone was loosely based on Anne and it has been speculated that Brontë originally planned to kill off Caroline but changed her mind because of her family tragedies. Shirley is what Brontë believed her sister, Emily Brontë, would have been if she had been born into a wealthy family.The maiden name of Mrs. Pryor is Agnes Grey, the name of the main character in Anne's first novel. She was based on Margaret Wooler, the principal of Roe Head School, which Brontë attended as both student and teacher.

The novel is set in and around the spen valley area of west Yorkshire. This area is known as "Shirley country" to some locals. In the novel, Brairmains is based on "the red house" in Gomersal; Mary Taylor lived here and was a friend of Charlotte. The house is now open as a museum. Fieldhead in the novel is based on the Elizabethan manor house, Oakwell Hall, which is also a museum.