At age 17, Gandil ran away from home to play ball in the rough-and-tumble towns along the Arizona-Mexico border. He supplemented his income by boxing in the local heavyweight division, picking up $150 a fight. He joined the White Sox in 1910, lasted part of a year, and was sold to Washington, where he remained until 1916. Gandil made the acquaintance of Sport Sullivan, a sports gambler and bookie. Sullivan had rich and powerful friends, and his friendships with ballplayers like Gandil were crucial to a World Series fixing scheme he planned to pull off.
Gandil rejoined the White Sox in 1917 as their regular first baseman, but he was a malcontent, and was later considered to be the ringleader of the 1919 WS fix. His contacts with Sullivan, Abe Attell, and Billy Maharg paved the way for the 1920 scandal. In that 1919 Series, Gandil batted a paltry .233 but committed only one error. Gandil refused to play for Charlie Comiskey in 1920, due to a salary dispute with the penurious owner. In 1921 he was banned from baseball by Commissioner Landis.
