He played in Major League Baseball (MLB) for the Kansas City Royals, Miami Marlins, and Cincinnati Reds.

After not making a plate appearance for four weeks, he hit a single to score Jarrod Dyson for the winning run to clinch the World Series, marking the first time in history that a player in his first at bat in a World Series delivered the Series-winning run.

[10] In 2017, Raúl A. Mondesí won the Royals' starting second baseman position, and Colón competed with Whit Merrifield for a role on the Opening Day roster.

[14] Colón spent the remainder of the season with the Triple–A New Orleans Baby Cakes, playing in 49 games and batting .302/.379/.376 with one home run, 13 RBI, and six stolen bases.

Colón was removed from the 40–man roster and sent outright to the Triple–A Louisville Bats on November 4, after which he subsequently elected free agency.

On February 10, 2021, Colón signed with the Kansas City Monarchs of the American Association of Professional Baseball.

[19] On April 24, 2021, Colón signed a minor league contract with the Toronto Blue Jays organization.

[22] On January 4, 2022, Colón was hired to serve as the assistant hitting coach for the Northwest Arkansas Naturals, the Double-A affiliate of his former team, the Kansas City Royals.