The England international is given his first start by manager Andre Villas-Boas since signing from Bolton, while De Gea and Rooney return for the title-chasing visitorsGary Cahill is handed his Chelsea debut in place of the injured John Terry and fit-again midfielder Michael Essien makes his first start of the season with Frank Lampard still out.
Jose Bosingwa replaces the suspended Ashley Cole at left-back, while Fernando Torres and Daniel Sturridge are chosen up front.
Ashley Young returns from injury for Manchester United as Sir Alex Ferguson makes six changes from the side which beat Stoke in midweek.
Wayne Rooney partners Danny Welbeck upfront while keeper David De Gea has recovered from illness to start.
Chelsea: Cech; Ivanovic, Cahill, David Luiz, Bosingwa; Essien, Meireles, Malouda; Sturridge, Torres, Mata.
Subs: Turnbull, Ferreira, Bertrand, Hutchinson, Romeu, Piazon, Lukaku.
Manchester United: De Gea; Rafael, Evans, Ferdinand, Evra; Valencia, Carrick, Giggs, Young; Rooney, Welbeck.
Subs: Amos, Berbatov, Park, Hernandez, Fabio, Scholes, Pogba.