Liverpool's 100% record in the Champions League was ended by a remarkable comeback from Dirk Kuyt's Fenerbahce
Alexander Isak came off the bench to restore Liverpool's lead midway through the second half after former Manchester United forward Mason Greenwood cancelled out Trey Nyoni's opener. However, two goals in quick succession from Englishman Archie Brown and Vedat Muriqi gave Fenerbahce a stunning victory inside a raucous Sukru Saracoglu stadium.
Kuyt, who previously played for Liverpool and Fenerbahce, has been serving as interim head coach of the Turkish side - with former Newcastle player Emre Belozoglu to take over on a permanent basis on Thursday. This turned into a special night for the Dutchman as Fenerbahce won for the first time in the Champions League this season.
Liverpool boss Andoni Iraola made five changes following the weekend defeat by Arsenal, with Bradley Barcola starting as the team's striker. Fenerbahce's starting XI boasted over 1,000 Premier League appearances between them, containing the likes of Ederson, Ngolo Kante and Romelu Lukaku.
Liverpool started strongly and led when Nyoni's volley took a deflection off Kojo Peprah Oppong and went past Ederson. It was the 19-year-old's first goal for the club and Liverpool's first goal against a Turkish side in Turkey since Kuyt scored against Trabzonspor in 2010.
The home side responded swiftly as Greenwood's free-kick deflected off Jeremy Jacquet and beat Alisson. Both managers turned to the bench after the break, with Iraola throwing on Isak, Florian Wirtz and Cody Gakpo. Gakpo and Isak combined to restore Liverpool's advantage, with the latter heading in from close range.
But a spirited Fenerbahce side drew level just four minutes later when Gakpo's header from Kante's cross took the ball away from Alisson and Brown tapped in from close range. Brown - born in Birmingham - then turned provider when Liverpool failed to deal with his cross and Muriqi headed into the right corner.
Liverpool have happy memories in Istanbul, winning the 2005 Champions League in the Turkish capital, but have now lost six consecutive games against Turkish sides here.