Up to 2,000 supporters will be permitted to attend a fascinating contest between two sides separated by four places but just one point in the Premier League table.
The whole country has been waiting nine months to welcome supporters back into stadiums, and Saturday marks a major milestone in the journey back to normality in the world of football.
The unfortunate reality is that some areas of England remain under stricter conditions than others, and so neither Burnley nor Manchester City will be able to welcome fans back in Saturday's earlier kickoffs, while the London Stadium is still likely to feel sparse and cavernous with only 2,000 of the 60,000 seats being filled.
It is nonetheless another step in the right direction, although West Ham have more reason than most to want to delay the return of supporters even longer having seen their home form improve since matches were played behind closed doors.
Indeed, the Hammers are the team with the most improved home form since lockdown, winning five of their last 10 such top-flight matches compared to only two of 10 beforehand, while Manchester United boast the most improved away form since lockdown - eight wins in nine compared to only three wins beforehand.
It all adds another intriguing layer to an already interesting battle between two sides whose form over the last five league games has been identical - a draw, a defeat and then three wins on the bounce.
For Manchester United, the latest of those victories was a rousing come-from-behind triumph over Southampton as they recovered from 2-0 down at half time to win 3-2 at St Mary's.
It has undoubtedly been an inauspicious start to the season for Ole Gunnar Solskjaer's men, but after a quarter of the season they are still only five points off the top of the table with a game in hand, and victory this weekend would lift them up into the top four temporarily at least.
The Red Devils have their away form to thank for that, with the win at Southampton making it eight successive league wins on their travels for the first time in their history.
Another triumph at the London Stadium would see them win their first five away games of a league season for the first time since 1985-86, having already become the first team in Premier League history to have won four successive away games despite conceding first in all of them.
Indeed, those 12 points won from losing positions is the most in the top flight this term, so they certainly will not panic if West Ham take the lead on Saturday, despite failing to overturn another deficit during Wednesday night's 3-1 home defeat to Paris Saint-Germain.
That result has left Manchester United's qualification hopes hanging by a thread heading into the final group game at RB Leipzig next week, but Solskjaer will know that his side must be fully focused on the Premier League this weekend as they visit a West Ham side in fine form.
While Man United have found themselves needing to come from behind on numerous occasions this season, West Ham have now scored the opening goal in each of their last five league games and could extend that run to six - something they have only achieved once before in the Premier League era.
David Moyes has led his team to three consecutive Premier League victories and just one defeat in their last eight top-flight outings - including taking points off league leaders Tottenham Hotspur, Manchester City, Leicester City and Wolverhampton Wanderers.
All of that means that victory in this match would temporarily take the Hammers up to third in the table, just one point off the leaders, and they have reason to be confident of doing exactly that having won five and lost none of their last six home outings across all competitions - most recently Monday night's 2-1 triumph over Aston Villa.
The Hammers did need to rely on a missed penalty and another highly-contentious VAR call to get that victory, but they have won their last two league home games against Man United and will firmly believe that they can make it three in a row for the first time since December 1977 even with their visitors' fine away form.
West Ham United Premier League form: DDLWWW
Manchester United Premier League form: WDLWWW
Manchester United form (all competitions): LWWWWL
Manchester United are hopeful that Marcus Rashford will be fit for this match despite the striker being forced off against PSG with a recurrence of his shoulder injury.
The number 10, who scored the Red Devils' goal in that match, switched to the right flank to accommodate Edinson Cavani in midweek, so if he misses out then it could be a straight swap for Mason Greenwood.
Cavani is still waiting to hear the result of an FA investigation into a social media post which could be deemed racist, but if eligible for this match he could lead the line once again having inspired the comeback against Southampton last weekend.
Indeed, the Uruguayan is averaging a goal or assist every 32 minutes in the Premier League this season, netting three times and creating one more in his 128 minutes on the field.
The main man remains Bruno Fernandes, though, with the Portuguese playmaker having now scored in each of his last five league away games. Another goal on Saturday would see him become the first Man United player to score in six on the bounce since Denis Law in March 1964.
The impact of Fernandes on the team has been enormous, with Man United earning more Premier League points per game than any other team since his arrival and picking up 17 more points overall in those 23 matches than they did in their previous 23 before that.
Saturday's match is likely to come just too soon for Luke Shaw, but United otherwise have a fairly clean bill of health with David de Gea, Alex Telles, Scott McTominay, Paul Pogba, Anthony Martial, Donny van de Beek, Jesse Lingard and Eric Bailly all overcoming doubts to feature in the matchday squad in midweek.
Antonio returned against Aston Villa but did not look fully fit and only lasted the first half, so he will miss out again with Sebastien Haller likely to come back into the starting XI.
West Ham United possible starting lineup:
Fabianski; Balbuena, Ogbonna, Cresswell; Coufal, Rice, Soucek, Masuaku; Bowen, Haller, Fornals
Manchester United possible starting lineup:
De Gea; Wan-Bissaka, Lindelof, Maguire, Telles; McTominay, Fred; Greenwood, Fernandes, Martial; Cavani
We say: West Ham United 2-1 Manchester United
This will be only the fourth time in the Premier League era that West Ham go into a match against Manchester United sitting above their opponents in the table, and we are backing Moyes to extend that lead against his former club.
Man United's away form is nothing short of incredible, but West Ham have been impressive at home, have fared relatively well against the bigger teams and should be boosted by the long-awaited return of supporters too.
Top betting tip
Watch the Sports Mole Football Shorts prediction for this game below: