Roberto Mancini suffered defeat in the Istanbul derby as Fenerbahce beat rivals Galatasaray 2-0 to go four points clear at the top of the table.
Former Galatasaray midfielder Emre Belozoglu opened the scoring with a 23rd-minute penalty.
Didier Drogba threatened for Galatasaray but Cristian Baroni's 66th-minute finish sealed their fate.
It was Galatasaray's second straight defeat after losing to FC Copenhagen in the Champions League last week.
Galatasaray's day to forget was summed up when Felipe Melo missed a last-minute penalty.
Former Manchester City boss Mancini had seen his side win three straight league games after losing 2-1 at Akhisar Belediyespor on 6 October.
But defeat leaves them nine points behind Fenerbahce in the table.