The defending champions, who have won all five of their matches, look to maintain their lead and widen the point gap against their historical rival.
Despite early disappointment in the Champions League, Galatasaray has proven itself a strong contender in the league, scoring 17 goals in five games, the most in the competition.
Both teams have minimal injuries, with Fenerbahce missing Osayi Samuel and Galatasaray without Hakim Ziyech.
The derby will mark coach Jose Mourinho's first in Türkiye, adding another chapter to his illustrious career of 78 derbies, where he has secured 40 wins, 18 draws and 20 losses.
His counterpart, Okan Buruk, has beaten Fenerbahce three times, with one win by default.
The last few encounters between the teams have been marked by red cards, with 46 shown across their previous 62 matches.
Referee Atilla Karaoglan will officiate the match which will kick off at 8 p.m. local time. Karaoglan's assistants will be Ceyhun Sesiguzel and Suleyman Ozay.
Tickets for the derby sold out immediately.
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