Pagnozzi attended Highland High School in Gilbert, Arizona, and then Central Arizona College. The St. Louis Cardinals selected him in the eighth round of the 2003 June amateur draft as the 245th pick overall.

Pagnozzi made his professional baseball debut with the New Jersey Cardinals of the New York–Penn League. By 2008, he had advanced to the Memphis Redbirds, the AAA affiliate of the St. Louis Cardinals. In September 2009, the Cardinals called him up to the major leagues when rosters expanded. He made his MLB league debut on September 29, 2009, appearing as a pinch hitter and drawing a walk. Pagnozzi hit his first major league home run on September 28, 2010, against the Pittsburgh Pirates.