The defeat is the latest in a string of poor results which has seen the Rams fall to 14th in the Championship, with just three wins in their season so far.
Clough was the longest-serving manager in the league but the owners decided he had taken the club as far as he was able.
"Derby County have this evening announced that they have parted company with manager Nigel Clough with immediate effect. 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," the club said in a statement.
"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 ownership group remain steadfastly committed to the club and maintain their desire to compete at the top end of the SkyBet Championship this season.
"The search is well underway to identifying and appointing a successor, and further announcements will be made in due course.
"The club would also like to take this opportunity to wish Nigel Clough well for the future."