Fullerton was born in Ohio and attended the Ohio State University. Fullerton reportedly never graduated from Ohio State. He was kicked out for unknown reasons (he never explained to his family). He was later honored by the university for his writing. He moved to Chicago to begin his career in journalism. Fullerton wrote in a colorful style, including slang and human interest elements for the first time in sports journalism. In fact, he is credited as the first writer to include quotes from players in sports coverage. Among his protégés were Ring Lardner and Grantland Rice.
Fullerton, however, was also adept at the details of the game of baseball, and made strong use of the predictive power of baseball statistics. He made a name for himself in 1906 by predicting that the weak-hitting Chicago White Sox would upset the crosstown-rival Chicago Cubs in that year's World Series. The Cubs had won 116 games that season and were favored to win; the White Sox batted an anemic .230 and hit a total of seven home runs. The White Sox won the Series four games to two.
Fullerton's prestige made him a powerful voice blowing the whistle on the Black Sox scandal. Prior to the 1919 World Series between the White Sox and the Cincinnati Reds, Fullerton received a tip from professional gamblers that the Cincinnati team was a lock to win. The scene immortalized in the 1988 film Eight Men Out indicated that Fullerton (portrayed by Studs Terkel) watched the series with the legendary Ring Lardner and together they counted suspicious plays. In actuality, Fullerton did this with former pitching great Christy Matthewson. Fullerton's series of articles, headlined "Is Big League Baseball Being Run for Gamblers, with Ballplayers in the Deal?", forced the baseball establishment to investigate the charges. One year later, the eight White Sox ballplayers who participated in, or knew of, the plot to throw the series were banned from the game for life.
Fullerton was also famous for writing stories about his hometown of Hillsboro, Ohio.