St. Louis announced the decision on Saturday night. Matheny, 47, took over as the Cardinals' skipper in 2012. He helped the Cardinals win the National League in 2013. Matheny posted a 591-474 record in more than six seasons as the Cardinals' manager.
"Mike Matheny has served the St. Louis Cardinals organization with tremendous dedication and pride, and I am thankful for his service to the Cardinals over the past six and a half seasons," Cardinals principal owner Bill DeWitt Jr. said in a statement. "On behalf of the entire Cardinals organization, I would like to wish Mike the very best."
The Cardinals also fired hitting coach John Mabry and assistant hitting coach Bill Mueller. Mike Shildt will serve as the club's interim manager. Matheny was under contract through 2020.
"These decisions are never easy, but we felt that a change in leadership was necessary as the team prepares to enter into the second half of the season," Cardinals president of baseball operations Mozeliak said. "I would like to thank Mike for his exceptional commitment and devotion to the Cardinals' organization, including many fond memories of our years working together."
The Cardinals (47-46) are in third place in the National League Central, 7.5 games behind the division-leading Chicago Cubs and 1.5 games above the fourth-place Pittsburgh Pirates. St. Louis has dropped back-to-back games to the Cincinnati Reds, entering Sunday's series finale at Busch Stadium.
The 11-time champions haven't reached the playoffs since the 2015 season and last won the World Series under Tony La Russa in 2011. La Russa managed the Cardinals for 16 seasons, leading the team to three pennants and two World Series titles.