Thomas Schneider has replaced Bruno Labbadia as coach while Serdar Tasci has left the club to join Spartak Moscow, ending a 14-year allegiance with a side he celebrated Bundesliga glory with in 2007.
"Serdar Tasci made a big name for himself during his time here," said Stuttgart's director of sport Fredi Bobic.
"He has known the club since he was a child and always identified fully with Stuttgart.
"He would now like to gain a new experience abroad after all of these years and develop further there.
"We wish Serdar all the best with his future and hope that he has at least as much success as he had with Stuttgart."
Tasci's departure leaves new coach Schneider with a selection headache and some improvisation to do at the back, while he must also lift his side's spirits after they were knocked out of the Europa League on Thursday night.
"I'm a positive person and straight after the game, I told my team that I could understand their disappointment, and that it was fine to feel that way for a day, but that it must be put behind them the day after," Schneider said at a press conference.
"We have now got to look forwards. I hope the team realise that because it's only natural that you lose games, but we need to turn our focus to our next opponents rather than complaining."
Their next opponents are Hoffenheim, who have made an unbeaten start to the season, unlike Stuttgart who have yet to pick up a point.
Hoffenheim coach Markus Gisdol believes that the change in coach at Stuttgart will make things harder for his side, however.
"We must not make the mistake of under-estimating them," he said. "We have no idea which Stuttgart players will be playing and that makes it even harder for us to assess."
Gisdol does not know which players he will pick yet either with Sebastian Rudy back in the frame after injury, but Sejad Salihovic is suspended.