Former United striker Javier Hernandez looks set to make his Hammers debut at Old Trafford, where he won two Premier League titles under Sir Alex.
'Chicharito' - who scored 59 goals in four seasons at United before he was sold in 2014 - joined Slaven Bilic's side for £16m from Bayer Leverkusen last month.
Looking to replicate their impressive seventh-placed finish from the Croatian's first campaign at the helm in 2015-16, West Ham have been active in this summer's window with four big-name signings.
Having endured a difficult first campaign at the Olympic Stadium in which they finished eleventh, Bilic has also brought in Marko Arnautovic from Stoke, and former City pair Joe Hart and Pablo Zabaleta.
All four new boys are available to start, but Michail Antonio, Manuel Lanzini, Diafra Sakho, Cheikou Kouyate and Andy Carroll are out injured.
The new Premier League season kicked off on Friday, and this 4pm kick off means that United and West Ham are the last two sides to get going - 84 days after our last top flight action.
Luke Shaw, Ashley Young and Marcos Rojo are all long-term absentees, but summer signings Victor Lindelof, Romelu Lukaku and Nemanja Matic are likely to be handed debuts for the Reds.
United won six out of their seven pre-season matches and lost narrowly in the Super Cup to Real Madrid on Tuesday.
Manager Jose Mourinho said his side enjoyed a "complete tour" and that the side are ready for the recommencing of domestic league duties.
He said: "The Premier League is what we all know, I would say there are seven teams to fight for the title and 20 teams to fight for the victory every weekend.
"The Premier League is different to any other league, and I worked in three of them so I know this.
"This season we have the Champions League as well, it is more difficult to win than the Europa League but the motivation is higher.
"If we get through the group stage, it is not difficult to motivate the team to play against Real Madrid, Barcelona, the top English sides, Bayern Munich.
"To be the champion in this country is the objective of every top team and top manager and of course that is what we want, our pre-season was very complete and I think we are ready."
United v West Ham, Old Trafford
Last time out: United 1-2 Real Madrid, Manchester City 3-0 West Ham
Match odds: United 7/2 Draw 9/2 West Ham 11/1
Referee: Martin Atkinson