The main events of the novel take place in the summer of 1922. Nick Carraway, a Yale graduate and World War I veteran from the Midwest – who serves as the novel's narrator – takes a job in New York as a bond salesman. He rents a small house on Long Island, in the (fictional) village of West Egg, next door to the lavish mansion of Jay Gatsby, a mysterious millionaire who holds extravagant parties but does not participate in them. Nick drives around the bay to East Egg for dinner at the home of his cousin, Daisy Fay Buchanan, and her husband, Tom, a college acquaintance of Nick's. They introduce Nick to Jordan Baker, an attractive, cynical young golfer with whom Nick begins a romantic relationship. She reveals to Nick that Tom has a mistress, Myrtle Wilson, who lives in the "valley of ashes": an industrial dumping ground between West Egg and New York City. Not long after this revelation, Nick travels to New York City with Tom and Myrtle to an apartment they keep for their affair. At the apartment, a vulgar and bizarre party takes place. It ends with Tom breaking Myrtle's nose after she annoys him by saying Daisy's name several times.
As the summer progresses, Nick eventually receives an invitation to one of Gatsby's parties. Nick encounters Jordan Baker at the party, and they meet Gatsby himself, an aloof and surprisingly young man who recognizes Nick from their same division in World War I. Through Jordan, Nick later learns that Gatsby knew Daisy from a romantic encounter in 1917 and is deeply in love with her. He spends many nights staring at the green light at the end of her dock, across the bay from his mansion, hoping to one day rekindle their lost romance. Gatsby's extravagant lifestyle and wild parties are an attempt to impress Daisy in the hope that she will one day appear again at Gatsby's doorstep. Gatsby now wants Nick to arrange a reunion between himself and Daisy. Nick invites Daisy to have tea at his house, without telling her that Gatsby will also be there. After an initially awkward reunion, Gatsby and Daisy reestablish their connection. They begin an affair and, after a short time, Tom grows increasingly suspicious of his wife's relationship with Gatsby. At a luncheon at the Buchanans' house, Daisy speaks to Gatsby with such undisguised intimacy that Tom realizes she is in love with Gatsby. Though Tom is himself involved in an extramarital affair, he is outraged by his wife's infidelity. He forces the group to drive into New York City and confronts Gatsby in a suite at the Plaza Hotel, asserting that he and Daisy have a history that Gatsby could never understand. In addition to that, he announces to his wife that Gatsby is a criminal whose fortune comes from bootlegging alcohol and other illegal activities. Daisy realizes that her allegiance is to Tom, and Tom contemptuously sends her back to East Egg with Gatsby, attempting to prove that Gatsby cannot hurt him.
When Nick, Jordan, and Tom drive through the valley of ashes on their way home, they discover that Gatsby's car has struck and killed Tom's mistress, Myrtle. Nick later learns from Gatsby that Daisy, not Gatsby himself, was driving the car at the time of the accident but Gatsby intends to take the blame anyway. Myrtle's husband, George, falsely concludes that the driver of the yellow car is the secret lover he recently began suspecting she has, and sets out on foot to locate its owner. After finding out the yellow car is Gatsby's, he arrives at Gatsby's mansion where he fatally shoots both Gatsby and then himself. Nick stages an unsettlingly small funeral for Gatsby, ends his relationship with Jordan, and moves back to the Midwest, disillusioned with the Eastern lifestyle.
- Nick Carraway – a Yale graduate originating from the Midwest, a World War I veteran, and, at the start of the plot, a newly arrived resident of West Egg, who is aged 29 (later 30). He also serves as the first-person narrator of the novel. He is Gatsby's next-door neighbor and a bond salesman. He is easy-going, occasionally sarcastic, and somewhat optimistic, although this latter quality fades as the novel progresses.
- Jay Gatsby (originally James "Jimmy" Gatz) – a young, mysterious millionaire with shady business connections (later revealed to be a bootlegger), originally from North Dakota. He is obsessed with Daisy Buchanan, a beautiful debutante, from Louisville, Kentucky whom he had met when he was a young military officer stationed at the Army's Camp Taylor in Louisville during World War I. Fitzgerald himself was actually based at Camp Taylor in Louisville when he was in the Army and makes various references to Louisville in the novel, including the Seelbach Hotel where the Buchanan party stayed while in town for Tom and Daisy's wedding. The character is based on the bootlegger and former World War I officer Max Gerlach, according to Some Sort of Epic Grandeur, Matthew J. Bruccoli's biography of F. Scott Fitzgerald. Gatsby is said to have briefly studied at Trinity College, Oxford in England after the end of World War I.
- Daisy Fay Buchanan – an attractive and effervescent, if shallow and self-absorbed, young Louisville, Kentucky debutante and socialite, identified as a flapper. She is Nick's second cousin, once removed; and the wife of Tom Buchanan. Daisy is believed to have been inspired by Fitzgerald's own youthful romances with Ginevra King. Daisy once had a romantic relationship with Gatsby, before she married Tom. Her choice between Gatsby and Tom is one of the central conflicts in the novel.
- Thomas "Tom" Buchanan – a millionaire who lives on East Egg, and Daisy's husband. Tom is an imposing man of muscular build with a "husky tenor" voice and arrogant demeanor. He is a former football star at Yale. Buchanan has parallels with William Mitchell, the Chicagoan who married Ginevra King. Buchanan and Mitchell were both Chicagoans with an interest in polo. Like Ginevra's father, whom Fitzgerald resented, Buchanan attended Yale and is a white supremacist.
- Jordan Baker – Daisy Buchanan's long-time friend with "autumn-leaf yellow" hair, a firm athletic body, and an aloof attitude. She is Nick Carraway's girlfriend for most of the novel and an amateur golfer with a slightly shady reputation and a penchant for untruthfulness. Fitzgerald told Maxwell Perkins that Jordan was based on the golfer Edith Cummings, a friend of Ginevra King. Her name is a play on the two then-popular automobile brands, the Jordan Motor Car Company and the Baker Motor Vehicle, alluding to Jordan's "fast" reputation and the freedom now presented to Americans, especially women, in the 1920s.
- George B. Wilson – a mechanic and owner of a garage. He is disliked by both his wife, Myrtle Wilson, and Tom Buchanan, who describes him as "so dumb he doesn't know he's alive." When he learns of the death of his wife, he shoots and kills Gatsby, wrongly believing he had been driving the car that killed Myrtle, and then kills himself.
- Myrtle Wilson – George's wife, and Tom Buchanan's mistress. Myrtle, who possesses a fierce vitality, is desperate to find refuge from her complacent marriage, but unfortunately this leads to her tragic ending. She is accidentally killed by Gatsby's car (driven by Daisy, though Gatsby insists he would take the blame for the accident).
- Meyer Wolfshiem[note 1] – a Jewish friend and mentor of Gatsby's, described as a gambler who fixed the World Series. Wolfshiem appears only twice in the novel, the second time refusing to attend Gatsby's funeral. He is a clear allusion to Arnold Rothstein, a New York crime kingpin who was notoriously blamed for the Black Sox Scandal which tainted the 1919 World Series.