Zaha's role sees him continue his leadership from the team's recent friendly with Millwall, when the Ivorian earned the captaincy mid-match.
He takes the place of Scott Dann, who is not in the squad, and as Luka Milivojevic starts on the bench.
Roy Hodgson has named Mamadou Sakho in Dann's place, with the centre-back making his first Premier League lineup since facing Wolverhampton Wanderers in July. He played competitive minutes midweek against AFC Bournemouth, scoring in the League Cup penalty shootout.
Another change from the Eagles' Southampton victory sees Ryan Inniss take Sam Woods' spot on the bench, with Inniss also facing the Cherries recently.
For United, Palace Academy graduate Aaron Wan-Bissaka is named on the bench, with another former Eagle, Timothy Fosu-Mensah, starting in the back four.
Bruno Fernandes returns to the side, with Mason Greenwood selected as a substitute.
United: De Gea, Lindelof, Maguire, Shaw, Fosu-Mensah, McTominay, Pogba, Fernandes, James, Martial, Rashford.
Subs: Henderson, Bailly, Wan-Bissaka, Van de Beek, Fred, Ighalo, Greenwood.
Palace: Guaita, Ward, Kouyaté, Sakho, Mitchell, Townsend, McCarthy, McArthur, Schlupp, Ayew, Zaha.
Subs: Hennessey, Kelly, Inniss, Milivojević, Eze, Meyer, Batshuyai.