Gaedel (some sources say the family name may actually have been Gaedele ) gained immortality in the second game of a St. Louis Browns doubleheader on Sunday, August 19, 1951. Weighing 65 pounds (29.5 kg), and standing 3 feet 7 inches (1.09 m) tall, he became the shortest player in the history of the major leagues. He made a single plate appearance and was walked with four consecutive balls before being replaced by a pinch-runner at first base. His jersey, bearing the uniform number "⅛", is displayed in the Baseball Hall of Fame.

Browns owner Bill Veeck was a showman who enjoyed staging publicity stunts. He found Eddie Gaedel through a booking agency. Due to his size, Gaedel had worked as a riveter during World War II. Gaedel was able to crawl inside the wings of airplanes. After the war, Gaedel was the promotional mascot for Mercury Records.

Gaedel was secretly signed by the St. Louis Browns and put in uniform (complete with elf slippers and the number "⅛" on the back). Gaedel came out of a papier-mache cake between games of a doubleheader to celebrate the American League's 50th anniversary, and as a Falstaff Brewery promotion. Falstaff, and the fans, had been promised a "festival of surprises" by Veeck. Before the second game got underway, the press agreed that the "midget-in-a-cake" appearance had not been up to Veeck's usual promotional standard. Falstaff personnel, who had been promised national publicity for their participation, were particularly dissatisfied. Keeping the surprise he had in store for the second game to himself, Veeck just meekly apologized.

Although Veeck denied the stunt was directly inspired by it, the appearance of Gaedel was unmistakably similar to the plot of "You Could Look It Up," a 1941 short story by James Thurber. Veeck insisted he got the idea from listening to the conversations of Giants manager John McGraw decades earlier when Veeck was a child.

Gaedel entered the second half of the doubleheader between the Browns and Detroit Tigers in the bottom of the first inning as a pinch-hitter for leadoff batter Frank Saucier. Immediately, umpire Ed Hurley called for Browns manager Zack Taylor. Veeck and Taylor had had the foresight to have a copy of Gaedel's contract on hand , as well as a copy of the Browns' active roster, which had room for Gaedel's addition.

The contract had been filed late in the day on Friday, August 17. Veeck knew the league office would summarily approve the contract upon receipt, and that it would not be scrutinized until Monday, August 20. Upon reading the contract, Hurley motioned for Gaedel to take his place in the batter's box. (As a result of Gaedel's appearance, all contracts must now be approved by the Commissioner of Baseball before a player can appear in a game.) The change to that day's St. Louis Browns scorecard, listing Gaedel and his uniform number, had gone unnoticed by everyone except Harry Mitauer, a writer for the St. Louis Globe-Democrat. The Browns' publicity man shunted Mitauer's inquiry aside.

Gaedel was under strict orders not to attempt to move the bat off his shoulder. When Veeck got the impression that Gaedel might be tempted to swing at a pitch, the owner warned Gaedel that he had taken out a million dollar insurance policy on his life, and that he would be standing on the roof of the stadium with a rifle prepared to kill Gaedel if he even looked like he was going to swing. Veeck had carefully trained Gaedel to assume a tight crouch at the plate; he had measured Gaedel's strike zone in that stance and claimed it was just one and a half inches high. However when Gaedel came to the plate, he abandoned the crouch he had been taught for a pose that Veeck described as "a fair approximation of Joe DiMaggio's classic style", leading Veeck to fear he was going to swing. (In the Thurber story, the midget cannot resist swinging at a 3-0 pitch, grounds out, and the team loses the game).

With Bob Cain on the mound - laughing at the absurdity that he actually had to pitch to Gaedel - and catcher Bob Swift catching on his knees, Gaedel took his stance. The Tigers catcher offered his pitcher a piece of strategy: "Keep it low." Cain delivered four consecutive balls, all high (the first two pitches were legitimate attempts at strikes; the last two were half-speed tosses). Gaedel took his base (stopping twice during his trot to bow to the crowd) and was replaced by pinch-runner Jim Delsing. The 18,369 fans gave Gaedel a standing ovation.

Veeck had hoped that Delsing would go on to score in a one-run Browns victory, but he ended up stranded at third base and the Tigers went on to win the game 6–2. American League president Will Harridge, saying Veeck was making a mockery of the game, voided Gaedel's contract the next day. In response, Veeck threatened to request an official ruling on whether Yankees shortstop and reigning MVP Phil Rizzuto was a short ballplayer or a tall midget.

Initially, major league baseball struck Gaedel from its record book, as if he had not been in the game. He was relisted a year later. Eddie Gaedel finished his major league career with an on-base percentage of 1.000. His total earnings as a pro athlete were $100, the scale price for an AGVA appearance. However, he was able to parlay his baseball fame into more than $17,000 by appearing on several television shows.