Scott McTominay was handed his first Premier League start of the season as Manchester United manager Jose Mourinho made four changes from last weekend's home draw with Wolves.
The young Scotland international is joined by Ashley Young, Nemanja Matic and Anthony Martial in being brought into the Reds' league line-up.
Young was on the bench when United faced Wolves, while Matic and Martial featured in the midweek Carabao Cup exit to Derby County.
As for McTominay, the 21-year-old has been a regular option on the bench for the manager this season, coming on as a substitute against Leicester City and Watford.
Speaking ahead of the game, Jose Mourinho had this to say to BT Sport about the contrasting weeks for his team and the opposition at the London Stadium:
“It was a week with two bad results for us and that could have been worse because we had two draws,” he said.
“But two draws at home are not good results. So it could be better, could be worse, it is what it is. Now it's in the past and in a few minutes we have a very difficult match against a team that had by opposite a good week with a very good victory and one important draw against Chelsea.
”So it's a difficult match for us but we believe in the work we did in the week and we are positive.
The Reds are so far unbeaten at the London Stadium with an away win and a draw since West Ham moved there from Upton Park. However, with the Hammers strengthening their squad over the summer with a number of marquee signings, Mourinho admitted that it will be another difficult contest.
“Today is away, in a beautiful stadium, with an amazing crowd and a difficult opponent,” he said.
“They are on a high, they made fantastic investment in the summer, so it's a difficult match for us but we also believe it's a difficult match for them.”
A win or a draw today would close out an undefeated month for Mourinho's men, who will be looking forward with anticipation to October which brings two tricky Champions League fixtures as well as a clash with Chelsea at Stamford Bridge in the league.
Naturally, everyone in the Reds camp wants to bring back three points from the capital.
“Of course,” he said.
“It's better to go to Euston [Train station] after a victory than after a defeat.”
United: De Gea; Young, Smalling, Lindelof, Shaw; Fellaini, Matic, McTominay; Pogba; Martial, Lukaku. Substitutes: Grant, Bailly, Darmian, Herrera, Fred, Mata, Rashford.