Fenerbahce's flawless start to the new campaign came to a screeching halt on Saturday night as suffered a 3-2 home defeat to Trabzonspor.
The Istanbul giants game into the tie with an unblemished record of 19 wins from 19 games in all competitions but were undone by the resilient away side.
Former Southampton forward Paul Onuachu broke the deadlock after just 10 minutes before a quick-fire double from Berat Ozdemir and ex-Arsenal winger Nicolas Pepe put the tie out of reach just after the break.
To Fenerbahce's credit they mounted a respectable comeback as Saints and Ajax oldboy Dusan Tadic hit back with two goals from the penalty spot, either side of a Ismail Yutsek sending off.