Zaha joins Scott Dann and Patrick van Aanholt in being absent from the squad in Hertfordshire today, with Jeffrey Schlupp filling the Dutchman's space at left-back.
Alongside him is Martin Kelly, who replaces Dann.
In midfield, Cheikhou Kouyate and Max Meyer have been selected as the replacements for Zaha and the repositioned Schlupp, with Michy Batshuayi starting up front.
All in all, then, Palace manager Roy Hodgson has made a total of three changes since his side lost to Brighton and five to the lineup which beat Doncaster Rovers in the last round of the cup.
On the bench, Connor Wickham finds himself in the squad for the first time since the Eagles' trip to Southampton at the end of January.
The hosts today have made seven changes to the side which was re-shuffled for a trip to Manchester City last Saturday, with Troy Deeney coming in for Andre Gray. In total, they have made six changes to their lineup in the last round of the cup, a 1-0 win over Queens Park Rangers.
Most notably, Kiko Femenia starts as he continues his recovery from a hamstring injury and Abdoulaye Doucoure, Roberto Pereyra and Gerard Deulofeu all start for the first time in the tournament.
Watford: Gomes, Mariappa, Feminia, Cathcart, Holebas, Hughes, Doucoure, Capoue, Pereyra, Deulofeu, Deeney.
Subs: Dahlberg, Kabasele, Janmaat, Masina, Cleverley, Success, Gray.
Palace: Guaita, Schlupp, Kelly, Tomkins, Wan-Bissaka, Milivojevic, Kouyate, Townsend, Meyer, McArthur, Batshuayi.
Subs: Hennessey, Woods, Ward, Riedewald, Wickham, Benteke, Ayew.
