He played in Major League Baseball (MLB) for the Atlanta Braves, Detroit Tigers, and Kansas City Royals.

Colón earned a win in his first Double–A start in a 3–1 victory against the Chattanooga Lookouts on April 9 (5 IP, 3 H, 1 R, 3 BB, 4 K).

He earned first career win on August 30 versus the San Francisco Giants with a scoreless ninth inning.

Colón had filled in admirably in an injury depleted Braves rotation in 2005, holding the Chicago Cubs to one run in seven innings on July 5.

The Detroit Tigers acquired Colón from the Braves (along with Zach Miner) in exchange for Kyle Farnsworth at the July 31, 2005, trade deadline.

[1] He spent most of his Tigers tenure in the bullpen before making two spot starts in September, and was shelved after that with stiffness in his throwing elbow.

During a rehab assignment with the Triple–A Toledo Mud Hens, he was involved in an altercation with fellow pitcher Jordan Tata.

According to his wife, who filed an assault report against Colón on her husband's behalf, Karnuth required a titanium plate to be screwed into his head.

On January 15, 2008, Colón pleaded no contest to an assault charge and was sentenced to 200 hours of community service.

[2] Colón was traded to the Kansas City Royals on July 13, 2007, for a player to be named later (minor league pitcher Daniel Christensen).

On January 12, 2011, Colón signed a minor league contract with the Los Angeles Dodgers, which included an invitation to spring training.

Colón signed a minor league contract with the Kansas City Royals on January 25, 2012, and received an invitation to spring training.

[9] He made 2 starts for the Triple–A Colorado Springs Sky Sox, allowing 7 unearned runs in 5+2⁄3 innings pitched.

In 15 games (2 starts) for the Brothers, Colón compiled a 2–4 record and 2.52 ERA with 14 strikeouts and 3 saves across 25 innings pitched.