Miñoso was signed by the Cleveland Indians as an amateur free agent in 1948. Between 1949 and 1964 he played for the Tribe (1949, 1951, 1958–59), Chicago White Sox (1951-1957, 1960–61, 1964, 1976, 1980), St. Louis Cardinals (1962) and Washington Senators (1963). On May 1, 1951, in a game against the New York Yankees in Comiskey Park, the speedy Miñoso became the first black player to wear a White Sox uniform (this occurred in game of Mickey Mantle's 1st major league home run). The first American-born black to appear with the White Sox was catcher Sam Hairston, on July 18, 1951. Minoso won the Sporting News Rookie of the Year Award in 1951, but in a controversial vote, was 2nd to Gil McDougald in the official BBWAA Rookie of the Year voting.
In his major league career, and despite not playing regularly until he was 28 because of his race, Miñoso hit for a .298 batting average, with 186 home runs, 1023 RBI, 1136 runs, 1963 hits, 336 doubles, 83 triples, 205 stolen bases, 814 walks and 192 hit by pitch. His career ended with a .389 on base percentage and a .459 slugging average, combined for a solid .848 OPS. He was a 7-time All-Star. For his excellence in left field, he received the Gold Glove Award three times. He led his league in triples and stolen bases three times each. Ten times he led his league in hit by pitch; Miñoso is 9th all-time in the category.
In 1976, after several years playing in Mexico, Miñoso returned to play three games with the White Sox. He picked up one single in eight at bats, becoming at age 53 the second-oldest player ever to get a base hit in the major leagues (Hall of Famer Jim O'Rourke was the oldest when hit safely at age 54 on September 22, 1904). Miñoso returned to appear in two more games with the Sox in 1980. His five stints with Chicago cemented his image as a local baseball icon for at least three generations of Chisox fans. When the last game was played at the old Comiskey Park on September 30, 1990, Miñoso was invited to present the White Sox lineup card to the umpires in the pregame ceremonies at home plate. He did so while wearing the new uniform debuted by the White Sox that day, his familiar number 9 on the back.
In his 1980 appearance at age 57, Minoso was the oldest player ever to play in the majors. He would have made an appearance in 1990 and become the only professional to play in six decades if Major League Baseball had not overuled the minor league Miami Miracles organization on the idea. However, at age 80, in 2003 appeared in a professional baseball game by drawing a walk for the independent minor-league St. Paul Saints, becoming the only player to appear professionally in seven different decades.
Minnie took part in the victory parade for the Chicago White Sox 2005 World Series Championship.
In November 2005, Miñoso's name was placed on a special ballot of Negro League players to be voted upon by a special committee of Negro Leagues historians and scholars, though he did not win induction. Miñoso remains on the Veterans Committee ballot for the Hall of Fame as of 2006.
- Number 9 retired by White Sox
- 7-time All-Star: 1951-54, 1957, 1959, 1960
- 3-time Gold Glove Award winner: 1957 (MLB), 1959-60 (AL)
- Five times in the top 10 of AL's MVP vote: 1951, 1953–54, 1957, 1960
- The Sporting News Rookie of the Year Award: 1951
- Led AL in triples: 1951, 1954, 1956
- Led AL in hits and games played: 1960
- Led AL in doubles: 1957
- Led AL in hit by pitch: 1951-54, 1956–60
- Led AL in sacrifice flies: 1960-61
- Led AL in stolen bases: 1951-53
- Baseball-Reference.com - Major league career statistics
- Baseball Hall of Fame candidate profiles: Negro League Committee and Veterans Committee
- Baseball Library
- The Baseball Cube
- The Top 100 Greatest Indians Roster
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