Jose Mourinho has made five changes from the side knocked out of the Champions League by Sevilla, with Sanchez missing out for the first time since arriving from Arsenal in January following 10 successive starts.
The decision comes following a number of underwhelming performances in a variety of starting positions after signing for the club in the swap deal which saw Henrikh Mkhitaryan leave for the Emirates Stadium.
Pogba remains on the bench, from where he made a second-half substitute appearance on Tuesday, and it is Scott McTominay who steps in to replace Maroaune Fellaini in the midfield.
Sergio Romero, Luke Shaw, Anthony Martial and Juan Mata also come in, with David de Gea, Ashley Young and Marcus Rashford dropping to the bench.
Mourinho will be keen for his side to get back to winning ways following Tuesday's setback and the days of rancour which have followed.
Manchester United: Romero; Valencia, Smalling, Bailly, Shaw; McTominay, Matic; Mata, Lingard, Martial; Lukaku. Subs: De Gea, Lindelof, Pogba, Sanchez, Rashford, Fellaini, Young.
Brighton & Hove Albion: Krul; Schelotto, Dunk, Duffy, Suttner; Kayal, Propper, Gross, Locadia, March; Ulloa. Subs: Maenpaa, Bruno, Goldson, Sanders, Izquierdo, Baldock, Murray.