The St. Louis Cardinals drafted Luke Gregerson in the 28th round of the 2006 MLB Draft but sent him to the San Diego Padres three years later as part of a deal for Khalil Greene. Gregerson made his major-league debut with the Padres in 2009 and appeared in 72 games. In five seasons in San Diego, Gregerson posted a 2.88 ERA and 1.092 WHIP.
After the 2013 season, the Padres dealt Gregerson to the Oakland Athletics where he appeared in 72 games while maintaining a 2.12 ERA in 2014. Gregerson became a free agent after the season, and the Houston Astros signed him to a three-year, $18.