Trembley was in his third season as the Orioles' manager, compiling a 187-283 record since being hired in June 2007.
Third base coach Juan Samuel will serve as interim manager, the team said on its website (http://baltimore.orioles.mlb.com).
The Orioles, with a Major League-worst 15-39 record, are off to their worst start since the 1988 team opened the season with 21 consecutive losses.
"The results on the field were not what any of us would have hoped for, and I understand that the organization felt the time was right to move in a different direction," he said in a statement.
Samuel, 49, played in the majors for 16 seasons, primarily as a second baseman. He was a three-time National League All-Star.
In his 27th year in professional baseball, Samuel has been the Orioles' third base coach for four seasons.
(Reporting by Gene Cherry in Raleigh, North Carolina. Editing by Steve Ginsburg)