On July 19, 2007, Fox was called up from Double-A Tennessee to the major leagues after shortstop César Izturis was traded to the Pittsburgh Pirates. Fox was called up with the intent that he would play first base, outfield, and be the third catcher. He made his major league debut on July 19, 2007, against the San Francisco Giants in a pinch hitting role and grounded into a double play. He had his first career hit on August 15 against Phil Dumatrait of the Cincinnati Reds, a double. Fox hit his first career home run on June 25, 2009 against Armando Galarraga of the Detroit Tigers. On August 29, 2009, Fox hit his first career grand slam against Bobby Parnell of the New York Mets.