On July 26, 2014, the St. Louis Cardinals signed Pierzynski to a major league deal. Later that day, he debuted for St. Louis with a 3-for-4 outing and an RBI, helping to defeat the Cubs 6–3. Former Boston teammate John Lackey soon arrived via trade, and Pierzynski caught him for the 19th time in 22 starts in 2014 when he debuted for the Cardinals on August 3. It was the pitcher's 150th career win. Pierzynski's first home run with St. Louis came in a loss to Baltimore on August 8. He hit .244/.295/.305 in 82 at-bats, mostly serving as a backup catcher to Yadier Molina. The Cardinals left Pierzynski off the playoff roster for the NLDS against the Dodgers, but added him for the NLCS against the Giants.