Cliff Pennington was drafted by the Oakland A's as the 21st overall pick of the 2005 Amateur Draft. Selected out of Texas A&M University, where he compiled a .346 career average during three seasons, Cliff quickly moved through the A's Minor League system.

A representative of the U.S. squad for the 2008 Futures Game, Cliff made his Major League debut on August 12, 2008. After finishing the 2009 season as the A's everyday shortstop, Cliff received the opening-day job for the 2010 season.