The Cardinals went 80–81 during the season and finished seventh in the National League, 16+1⁄2 games behind the eventual World Series champion Los Angeles Dodgers.

Schoendienst's replacement of Keane had been preceded a few weeks earlier by general manager Bing Devine's firing, the redemption of the final pennant drive having come too late to assuage owner August Busch's dwindling patience.

Devine was replaced by Bob Howsam, who made a number of moves to shore up a talented but aging team which struggled through the 1965 campaign, finishing mired in 7th place at 80–81.

Howsam traded aging veterans Bill White, Dick Groat, and utility catcher Bob Uecker to Philadelphia in return for Pat Corrales, Art Mahaffey, and Alex Johnson.

Pitcher Bob Gibson, first baseman Bill White, and outfielder Curt Flood won Gold Gloves this year.