"It is the most difficult situation in the club's Bundesliga history," club president Erwin Staudt told reporters. "We looked for solutions with the coaching staff but after a lot of discussions with the board we decided to go our separate ways."
Assistant coach Jens Keller has taken over until the end of the season with the task of keeping Stuttgart in the top flight.
"Our focus is to remain in the Bundesliga. This is why the team around Keller will receive our full backing," Staudt said.
Stuttgart have picked up just three points from their opening seven league games.
Gross, the former FC Basel and Tottenham Hotspur coach, succeeded Markus Babbel at the helm in December 2009 and guided the side from the relegation zone to a Europa League berth.
Despite a good run in Europe, where they currently top Group H, Stuttgart have lost all but one Bundesliga match so far.
"I did not hesitate for a second when I was asked last night if I could imagine taking over," the 39-year-old Keller said during his official presentation.
"The team has enough potential to push themselves out of the dirt. There is not a lot of time before the Schalke game (on Saturday) so we need to get started," he said.
Schalke are only one place and one point above Stuttgart in the 18-team league and just as desperate for a win.
