Erik ten Hag, who is hoping to see his Red Devils side end a five-game winless run in all competitions, has made a total of three changes to the team that played out a 0-0 draw with Aston Villa prior to the international break.
Matthijs de Ligt and Lisandro Martinez have both been recalled to start in central defence at the expense of injured defender Harry Maguire and full-back Noussair Mazraoui, who is fit to make the substitutes' bench despite recently undergoing a minor heart procedure.
Both De Ligt and Martinez will provide protection for goalkeeper Andre Onana, while Jonny Evans is set to operate at left-back - as previously reported - with Diogo Dalot moving over to the right side of a back four.
The only other change made to Ten Hag's XI sees injured midfielder Kobbie Mainoo replaced by Casemiro, who will link arms with Christian Eriksen in the middle of the pitch as captain Bruno Fernandes continues in the number 10 role.
Alejandro Garnacho has been passed fit to start on the right flank, with Marcus Rashford keeping his spot on the left, while Rasmus Hojlund is preferred ahead of Joshua Zirkzee to the lead the line.
Manuel Ugarte picked up an injury on international duty with Uruguay earlier this week, but he is fit to make the bench, which also includes 17-year-old Jack Fletcher, the son of former Man United midfielder Darren Fletcher.
As for Brentford, Thomas Frank has named an unchanged starting lineup to the one that secured a 5-3 victory at home to Wolverhampton Wanderers in their most recent match prior to the international break.
A back three of Sepp van den Berg, Ethan Pinnock and Nathan Collins remains intact, with Kristoffer Ajer and Keane Lewis-Potter set to operate as wing-backs.
Christian Norgaard and Mikkel Damsgaard are both fit to start in centre-midfield alongside Vitaly Yanelt, while Yoane Wissa has recovered from an ankle injury sooner than expected, but he will begin as a substitute as in form-attacker Bryan Mbeumo will be joined up front by Kevin Schade.
Manchester United starting lineup: Onana; Dalot, De Ligt, Martinez, Evans; Casemiro, Eriksen; Garnacho, Fernandes, Rashford; Hojlund
Subs: Bayindir, Lindelof, Mazraoui, J. Fletcher, Ugarte, Amad, Antony, Wheatley, Zirkzee
Brentford starting lineup: Flekken; Van den Berg, Pinnock, Collins; Ajer, Janelt, Norgaard, Damsgaard, Lewis-Potter; Schade, Mbeumo
Subs: Valdimarsson, Wissa, Carvalho, Mee, Yarmoliuk, Meghoma, Konak, Trevitt, Roerslev