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In the novel, the settings relate to the themes of the book, in addition to providing a backdrop against which the reader can imagine the characters. The main action of the book takes place in and around Long Island, New York. However, there are flashbacks and many references to the Midwest. The main characters in the book all originate from this area. The narrator, Nick Carraway describes the book as:

a story of the West…Tom and Gatsby, Daisy and Jordan and I, were all Westerners

Nick says he comes from a "Middle-Western city", which may be assumed to be Minneapolis in Minnesota, although it is never named.

Tom Buchanan comes from Chicago and he and Daisy lived there before moving East.

The Midwest of America is associated with an upright, conservative lifestyle and strong family values. By the 1920s, Midwestern society had remained unchanged for generations. Nick describes his city as one where "dwellings are still called through decades by a family's name". While this creates a secure environment, it can also appear stifling and old-fashioned, e.g. he describes "all my aunts and uncles" talking over his change of career. He had been educated in New England and had been to Europe during the First World War. When he came back, the Midwest seemed to him "like the ragged edge of the universe".

However, Nick comes to appreciate his own area after becoming disgusted with the soulless immorality of the East. He recalls how much he enjoyed the "sharp wild brace" of the cold air when returning home at Christmas. After his involvement with the events of summer 1922, Nick turns his back on the East.

Gatsby also comes from the Midwest, specifically North Dakota, a relatively poor, agricultural area on the northern edge of the Midwest. He too abandons it in favour of the more glamorous East.