The two-time German champions are 13th in the table at the halfway stage of the league and sit just four points off the relegation play-off place.
Following their 2-1 defeat to Freiburg last time out, speculation intensified around the German's position, with the club confirming his exit on Friday.
Slomka, who was appointed by the club in 2010, secured the club their Bundesliga status in his first season after spending much of the season in the drop zone.
He then guided the club to a fourth-place finish in his second season - thereby qualifying for the UEFA Europa League - before finishing seventh and ninth in his next two campaigns.
"We have not made our decision lightly but together we have the conviction to want to change something," said sporting director Dirk Dufner in a statement on the club's official website.
Dufner will look to find a new head coach in the coming days, with president Martin Kind adding that the club would be forever grateful to Slomka for his work at the HDI-Arena.
"My personal thanks to Mirko Slomka," he said.
"He has saved Hannover 96 from relegation to the Bundesliga 2 and then led us into the UEFA Europa League twice. These successes will always be closely associated with his name."
