Third-base coach Dave Clark will take over as manager on an interim basis for the rest of the season.
Going into Monday night's game versus the NL Central-leading St. Louis Cardinals, the Astros were in fourth place, 16.5 games back, with a record of 70-79.
"Cecil Cooper has given his all to the Houston Astros," General Manager Ed Wade said. "Decisions like this are never easy, but we believe that a change in direction on the field is in order. By making the move today, we will have the ability to evaluate other facets of our operation as we move into the offseason."
Cooper, 59, had managed the Astros since August 27, 2007, in which he compiled a 171-170 record. Prior to being named manager, Cooper had served as the team's bench coach since the start of the 2005 season.
Clark, 47, is in his first season on the Astros coaching staff. He has never managed at the major league level, but he was manager of the Round Rock Express (AAA) in 2008 and manager of the Corpus Christi Hooks (AA) from 2005-2007. Clark also managed in the Pirates system in 2004.
Astros Minor League Field Coordinator Al Pedrique will replace Clark as third base coach for the rest of the season. He will resume his field coordinator duties after the season.
GM Wade said a search for the Astros new manager will be conducted in the offseason and that Clark will be considered as a candidate. He also said next season's coaching staff will be determined once the new manager is hired.
