Upon its publication in 1936, Gone with the Wind became an immediate best-seller. Before it even hit the bookstores, it was named as a Book of the Month main selection. In six months it sold a record-breaking one million copies and was well on its way to becoming the best-selling novel in history. To date it has outsold every other book except the Bible. The fervor it created extended to Mitchell herself, who quickly found that she could not leave home without fans begging her for autographs. Newspaper publishers and magazine editors offered her amazing sums for anything she would care to write for them. Hundreds of fan letters arrived at her home each day and her phone rang off the hook. Gone with the Wind was a national phenomenon.

Early reviews of the work spanned a wide range of opinions, but most were favorable. Many critics praised Mitchell for her attention to historical detail, her vivid characterization, and ear for dialogue. She was lauded as a gifted storyteller who held her readers spellbound. Edwin Granberry of the New York Sun compared her talent to that of the great Russian and English panoramic novelists, a comparison that other reviewers would draw as well. Herschell Brickell of the New York Post declared it the best novel written about the Civil War and its aftermath; furthermore, he predicted that Gone with the Wind would find a permanent place in American literature. In contrast, other critics dismissed the book as trite, overly sentimental, and full of cliches. Bernard DeVoto of the Saturday Review of Literature fell into this camp, deriding Gone with the Wind for its cheap sentiments, which he felt falsified true experience. In addition, there were reviewers who found aspects of the novel morally offensive. As Anne Edwards notes in her book, Road to Tara: The Life of Margaret Mitchell, some reviewers criticized Gone with the Wind for its "condescending portrait of blacks, the glorification of plantation life, and its lack of a political and social point of view."

In 1937, Gone with the Wind was honored twice: first with the Pulitzer Prize for fiction, and second with the annual prize for best fiction from the American Bookseller's Association. Following the release of the film in 1939, critical interest in the book virtually ended. Academics have since speculated that because Gone with the Wind was stylistically at odds with the modern literature published at the time and didn't fit easily into any school of literature, it was difficult for critics to assess. In addition, the novel's marketplace success and subsequent status as a pop culture icon has always been problematic, eclipsing everything else about the book for many critics. A resurgence of interest in the book occurred in the 1970s, but little consensus on its literary merit has been reached and criticism on it is still limited.

Mitchell herself admitted to being mystified by the book's mass appeal. Articles discussing the book's popularity appeared with some regularity in newspapers and magazines for a few years. Although several theories were debated, many reviewers attributed the book's success to the fact that Americans living through the Great Depression could readily identify with Scarlett's trials as she overcomes poverty and rebuilds her life in the Reconstruction South. But that seems only part of the book's allure, which continues to sell 250,000 paperback copies in the United States each year. As southern writer Pat Conroy expressed in his preface to the 60th anniversary edition of Gone with the Wind: "[The novel] works because it possesses the inexpressible magic where the art of pure storytelling rises above its ancient use and succeeds in explaining to a whole nation how it came to be this way. There has never been a reader or a writer who could figure out why this happens only to very few books…[Gone with the Wind] allows you to lose yourself in the glorious pleasure of reading itself, when all five senses ignite in the sheer happiness of narrative."