He played in Major League Baseball for the Tampa Bay Devil Rays, New York Mets, Houston Astros, Boston Red Sox, and Cleveland Indians from 1999 through 2012.

After the Devil Rays, he played for the New York Mets, who traded him to the Houston Astros for minor leaguer Adam Seuss in 2004.

On October 19, 2005 during the National League Championship Series he recorded the last out at Busch Memorial Stadium in St. Louis, Missouri, a fly ball which was caught by Astro Jason Lane in right field off the bat of Yadier Molina.

On July 28, 2007, Wheeler was traded back to the Tampa Bay Devil Rays in exchange for third baseman Ty Wigginton.

[2] Wheeler was designated for assignment immediately following the game on May 13, 2012, against the Boston Red Sox in which he gave up six earned runs in one inning.