McLouth continued to advance steadily through the minors, and on June 29, 2005, he made his major league debut, only a day after he was named an International League All-Star. As a result of an injury to starting center fielder Chris Duffy, McLouth received a substantial amount of playing time through the end of the season. In 109 at-bats, he compiled a .257 batting average, a .305 on-base percentage, and a .450 slugging percentage. McLouth made the Pittsburgh Pirates 2006 opening day lineup as a backup outfielder, sending outfielder Jody Gerut to start the year in Triple-A. At the start of the 2007 season, McLouth changed his uniform number from 59 to 3.