Hiram Bithorn played winter ball for his home team Senadores de San Juan. When San Juan manager Juan Torruella resigned only two weeks into the 1938 season, the Senadores chose 22-year-old Bithorn as their new skipper, making him the youngest manager in Puerto Rican Professional Baseball League history. Within three years, Bithorn was pitching at Wrigley Field. Bithorn was drafted by the Chicago Cubs in September 1941 and debuted in the Major Leagues on April 15, 1942, making history as the first Puerto Rican big leaguer. Bithorn won nine games and lost 14 in his first season, but he rebounded in 1943 by going 18–12 with an earned run average of 2.60 and completing 19 of his 30 starts, leading the league in shutouts with seven, establishing a record for Puerto Rican pitchers that still stands to this day. During this time, he also formed the second Latin American pitcher-catcher combination along with Cuban Chico Hernández. After his second season, Hiram Bithorn fought for the United States military in World War II. His promising start, though, did not last once he returned from military service. By this moment his weight had risen to 225 pounds, which led to rumors that he may not have the same abilities. Upon returning from the war, he returned to the Chicago Cubs, and went 6–5 in 1946. On January 25, 1947 he was purchased by the Pittsburgh Pirates only to be waived later. On March 22 of the same year, the Chicago White Sox selected him off waivers but only pitched two innings, developing a sore arm that ended his career. In a four-season career, Bithorn posted a 34–31 record with a 3.16 ERA in 105 pitching appearances (53 as a starter), including 30 complete games, eight shutouts and five saves, striking out 185 batters while walking 171 in 509⅔ innings of work.

At age 35, Bithorn tried to make a comeback in the Mexican Pacific League. Nevertheless, he was shot by police officer Ambrosio Castillo Cano on December 28, 1951 in El Mante, Tamaulipas, Mexico. Hiram Bithorn then was transferred to Ciudad Victoria’s hospital, where he died the next day. Initially, officer Castillo Cano claimed that Bithorn was violent and also admitted to being part of a communist cell and that he was on an important mission. Eventually this argument was debunked in court and Castillo Cano was sentenced to eight years in prison for Bithorn’s murder. Hiram Bithorn’s achievement of making it to the majors remained a source of pride in Puerto Rico, and he was honored in 1962 when the biggest ballpark on the island was built and named after him. Hiram Bithorn Stadium is located next to Roberto Clemente Coliseum and across the street from Plaza Las Américas Mall, the stadium has also hosted world championship boxing fights, the 1979 Pan American Games, and important musical spectacles. The Montreal Expos played 22 home games there in the 2003 and 2004 MLB seasons, while Rounds 1 and 2 of the 2006 and 2009 World Baseball Classic editions also were played there, including teams from Group C and Group D. In 2013 the World Baseball Classic Round 1, Pool C was played in the stadium, featuring Dominican Republic, Puerto Rico, Spain and Venezuela national teams.