Guéhi replaces Chris Richards in defence, who drops to the bench; Joachim Andersen, Tyrick Mitchell and Joel Ward complete the back-four.
In midfield, Cheick Doucouré is accompanied by Will Hughes as Jefferson Lerma continues to miss out through injury, while Ebere Eze starts further forwards.
Odsonne Edouard, who already has five goals this season, leads the line flanked by Jordan Ayew – who has recovered from a knock at Villa Park – and Jeff Schlupp.
Jean-Philippe Mateta is among the attacking reinforcements on the bench, alongside young prospects Jesurun Rak-Sakyi and Malcolm Ebiowei.
Palace: Johnstone (GK), Ward, Guéhi, Andersen, Mitchell, Doucouré, Hughes, Eze, Schlupp, Ayew, Edouard.
Subs: Henderson (GK), Matthews (GK), Holding, Mateta, Clyne, Ebiowei, Richards, Riedewald, Rak-Sakyi.
Fulham: Leno (GK), Reed, Jiménez, Ream, De Cordova-Reid, Pereira, Willian, Castagne, Palhinha, Diop, Robinson.
Subs: Rodák (GK), Bassey, Wilson, Cairney, Ballo-Touré, Muniz, Iwobi, Vinícius, Francois.