Pie got his first major league hit on April 17, 2007, a double off Greg Maddux of the San Diego Padres. He scored his first run in the same inning on a Derrek Lee hit. In the same game, Pie also threw a runner out at home plate from center field which gave the Cubs a chance to win the game. On April 23, Pie changed his number from 17 to 20. Pie recorded his first major league home run on April 27, 2007, off Anthony Reyes of the St. Louis Cardinals. Pie was sent back down to the minors, but he was recalled on June 3, 2007 and remained with the club until July 13, when he was sent back down to Triple-A to get more regular at-bats. However, the Cubs recalled Pie from the minors in order to replace an injured Alfonso Soriano and Ángel Pagán on August 8, 2007. On August 9, Pie was brought back up to Chicago.
When the Cubs traded their starting left-handed center fielder Jacque Jones in November 2007, general manager Jim Hendry indicated that the club wasn't necessarily looking outside for a veteran, with Pie and Sam Fuld in the mix. Fuld pushed Pie for the center field spot during spring training (Piniella in late February said that Pie was only "a head or nose in front" of Fuld). "He's ready to go out there in spring training lined up next to Pie and compete to play center field", Hendry said of Fuld. Pie fell victim to the spring training 2008 injury bug that afflicted the Cubs. Originally deemed "a minor surgery on the groin region", Cubs.com reported the injury as "a twisted testicle", an injury more commonly known as testicular torsion. The surgery involved sewing the outer layer of the testicle to the scrotum wall. The surgery was deemed successful, and Pie reported back to spring training.