The announcement was made on Saturday evening following the Rams' 1-0 away defeat to Nottingham Forest in the Championship.
"Derby County have this evening announced that they have parted company with manager Nigel Clough with immediate effect," read a statement on the club's official website.
"Clough has been in charge at the Rams since January 2009 and the club would like to place on record their thanks to him for his tireless efforts to bring stability to Derby County, and his hard work and dedication throughout his tenure.
"However, after much consideration, the board feel it is time to move Derby County forward to the next level, which will necessitate a comprehensive review of the club's football operations."
The defeat on Saturday left Derby 14th in the table with 11 points from nine matches.