Jay Bruce's professional career began in 2005 in the GCL playing for the Reds' lowest rookie team. For the 2007 season, Bruce was placed with the Reds high-A team, the Sarasota Reds, then quickly promoted to the Red's AA team, the Chattanooga Lookouts. He was selected to the 2007 All-Star Futures Game. Bruce was then promoted to the Reds' AAA club, the Louisville Bats, where he ended the season by winning Baseball America's Player of the Year title. During the Cincinnati Reds' final game of the 2007 season, Bruce was recognized for winning the Minor League Player of the Year award.

On May 27, 2008, the Reds organization called Bruce up and he made his major league debut. Bruce had an astounding 1.000 slugging percentage after his first six games. The only Major League player since 1969 to achieve a higher slugging percentage after his first six games was Mike Jacobs in 2005, with a mark of 1.050.

On December 9, 2010 the Reds agreed to extend Bruce to a 6 year deal and it includes an option for a seventh year. He was selected to the 2012 MLB All-Star game.