Old Trafford was for years regarded as a fortress for Manchester United under the guidance of Sir Alex Ferguson.
But perhaps now, after an indifferent 2013/14 campaign, there is an air of vulnerability about the Red Devils.
Here, whufc.com takes a look at six memorable away wins for West Ham against Saturday's opponents.
Manchester United 0-1 West Ham United
Barclays Premier League
13 May 2007
West Ham travelled to newly-crowned Champions Manchester United on the final day of the 2006/07 season needing a point to be sure of their Premier League status.
As it was, the Hammers took all three points thanks to Carlos Tevez, who scored on the stroke of half-time, placing his shot past Edwin Van der Sar after exchanging passes with Bobby Zamora.
The visitors were able to hold out in the second half as they ensured top-flight football would be played at the Boleyn Ground for another season.
Manchester United 0-1 West Ham United
Premier League
8 December 2001
West Ham inflicted a third straight league defeat on the Red Devils as a single goal from Jermain Defoe was enough to earn them all three points.
The defining moment came with 64 minutes on the clock as the diminutive striker headed home unchallenged at the far post following excellent work by Paolo Di Canio.
Visiting keeper David James then made a string of fine saves to keep his side in front and earn himself a precious clean sheet.
Defoe leaps to head home Di Canio's cross
Manchester United 0-1 West Ham United
FA Cup Round Four
28 January 2001
A game famous for the antics of United's eccentric French goalkeeper, Fabian Barthez, saw the Hammers through to the fifth round of the FA Cup.
76 minutes had elapsed when Paolo Di Canio bore down on goal with Barthez stood, one hand aloft, appealing in vain for an offside decision which never came.
The Italian proceeded to slot the ball past the Frenchman, leaving the Red Devils and their bemused fans out of the FA Cup.
Manchester United 2-3 West Ham United
First Division
25 August 1986
The second game of the 1986/87 season saw the Hammers rise to the top of the first division with an entertaining win over Manchester United.
A goal from Alan Devonshire and two from Frank McAvennie steered the away side to their second successive win at Old Trafford.
United did however to go onto finish four places above West Ham, ending the season in eleventh place.
McAvennie celebrates scoring in his heyday
Manchester United 0-2 West Ham United
FA Cup round five replay
9 March 1986
The Hammers had disposed of Ipswich and Charlton to earn a fifth round tie with Manchester United.
After a 1-1 draw four days earlier the visitors eased through to the sixth round thanks to a trademark penalty from Ray Stewart and a goal from Geoff Pike.
The cup run was halted just three days later in the next round, as a 2-1 defeat to Sheffield Wednesday sent the Hammers crashing out.
Manchester United 0-2 West Ham United
First Division
27 November 1976
West Ham had suffered eight defeats out of nine games before they journeyed to Old Trafford lying in a precarious 22nd place in the league.
Billy Jennings and Trevor Brooking were the heroes in claret and blue as they eased the mounting pressure on the Club.
By the end of the season the Hammers had managed to stabilise and finished the campaign in 17th place.