After a couple of years in the minor leagues, he made his major league debut on July 15, , as a pinch hitter against the Arizona Diamondbacks. His first major league hit on July 19 (against San Francisco Giants closer Brian Wilson) came exactly 24 years to the day of his father's first major league hit — both doubles. Towards the end of the 2006 campaign, Gwynn received more playing time, replacing Brady Clark in the lineup. He appeared in 32 games for the Brewers in 2006, hitting .260 and made the Brewers' opening day roster for .