Calderón was signed by the Seattle Mariners as an amateur free agent on July 30, 1979 and made his debut on August 10, 1984. Midway through the 1986 season he was traded to the Chicago White Sox, where he became an every-day rightfielder in 1987.
Known for his power and speed, Calderón put together a series of productive seasons in Chicago. He was sent to the Montreal Expos after the 1990 season, in a deal that brought Tim Raines to the White Sox. The Expos raised his yearly salary to over US$2 million a season, and his efforts were rewarded with a place on the 1991 NL All-Star team. Injuries the following season slowed him down, and after stints with the Boston Red Sox and again with the White Sox, he quit in 1993, at age of 31.
Calderón was a career .272 hitter with 104 home runs and 444 RBI in 924 games.