The 21-year-old winger signed from Rennes just over a week ago and watched on as an unused substitute in last Sunday's 2-1 win at Sheffield United.
However, Pep Guardiola has decided to hand Doku his first start for the Citizens this afternoon, while fellow new recruit Matheus Nunes - who join from Wolverhampton Wanderers on transfer deadline day - is named on the substitutes' bench.
Guardiola - who remains in Barcelona recovering from back surgery as Juanma Lillo fills in on the touchline - has made a total of three changes to the side that beat Sheffield United, with Doku, Phil Foden and Manuel Akanji all handed starts, the latter of whom returning to the matchday squad after recovering from illness.
Jack Grealish misses out due to injury, while Bernardo Silva and Josko Gvardiol are among the substitutes after starting against Sheffield United.
Kyle Walker will wear the captain's armband and joins Akanji, Ruben Dias and Nathan Ake in the back four, protecting Ederson between the stick.
Rodri and Mateo Kovacic will continue to link arms in centre-midfield, while Doku, Foden and Julian Alvarez will all support Erling Haaland in attack.
As for Fulham, Marco Silva has made four changes to the side that beat Tottenham on penalties in the EFL Cup second round on Tuesday, with Bernd Leno, Harry Wilson, Andreas Pereira and Raul Jimenez all coming into the first XI.
Key midfielder Joao Palhinha is not involved in the matchday squad after seeing a proposed transfer to Bayern Munich collapse yesterday, while Marek Rodak, Adama Traore and Rodrigo Muniz all drop to the bench after starting in midweek.
Willian returns to matchday squad after recovering from a knock, while new signing Timothy Castagne is in contention to make his debut off the bench, but Fode Ballo-Toure - who joined on loan from AC Milan yesterday - was not registered in time and therefore misses out.
Manchester City: Ederson; Walker, Dias, Akanji, Ake; Rodri, Kovacic; Foden, Alvarez, Doku; Haaland
Subs: Ortega, Carson, Phillips, Bernardo, Gomez, Gvardiol, Nunes, Bobb, Lewis
Fulham: Leno; Tete, Diop, Ream, Robinson; Reed, Cairney; Wilson, Pereira, De Cordova-Reid; Jimenez
Subs: Rodak, Bassey, Castagne, Francois, Traore, Willian, Muniz, Vinicius, Harris