Jocketty's assistant, John Mozeliak, was named interim general manager. Jocketty had one year remaining on his contract and his departure came one year after the Cardinals won the World Series. They posted a 78-84 record this season.
He had held the post for 13 years, during which St. Louis won six division titles and appeared in the World Series twice.
"Walt will be remembered as the Cardinals' GM during one of the most successful and memorable periods in team history and we will always be extremely grateful for his contributions to our many triumphs over the past 13 seasons," said Bill DeWitt Jr., the team's chairman of the board.
Manager Tony La Russa's contract expired at the end of the season and he has been asked to stay. He has yet to make a decision.