Moore was sent to the Chicago Cubs as one of four players traded for pitcher Kyle Farnsworth in 2005. Moore made his major league debut on September 4, 2006, against the Pittsburgh Pirates. He was called up again on July 20, 2007 to start at first base against the Arizona Diamondbacks after a suspended Derrek Lee and an injured Daryle Ward left the Cubs in need of a first baseman. Moore was sent down on July 24 after the suspension of Lee ended.
On August 31, 2007, Moore was traded from the Cubs to the Baltimore Orioles along with pitcher Rocky Cherry for starting pitcher Steve Trachsel.