From 2000 to 2003 Spiezio played for the Anaheim Angles. He played for the Seattle Mariners from 2004 to 2005 and for the St. Louis Cardinals from 2006 to 2007. During his career Spiezio won two World Series Championships in 2002 with the Angels and in 2006 with the Cardinals. He had issues with substance abuse and played in the independent Golden Baseball League. In April 2015 it was reported that Spiezio was tased and arrested after smashing a neighbor’s window.