The man who masterminded a shock FA Cup defeat of Ron Atkinson's side when United were the holders back in 1984 will again be plotting the Reds' downfall at Loftus Road this weekend.
Although Sir Alex has enjoyed the advantage in the head-to-head clashes, there have been some painful moments too as we select some of the key encounters:
Fickle fortune: West Ham 1 United 1, 1995:
The final-day match etched into Reds folklore; the soul-sapping fight in vain against fate. The final whistle prompted tears on the field among his players, but Sir Alex merely shook Redknapp's hand and beckoned his sweat-soaked heroes into the dressing room.
The King and ire: West Ham 0 United 1, 1996:
A hard-fought January win provided the shot in the arm for an unlikely surge to the league crown. Almost a year to the day after his Selhurst Park faux-pas, Eric Cantona not only took the points but demonstrated his rehabilitated character with an unlikely display of peacemaking.
P4 W2 D1 L1 GF5 GA3
West Ham (1994-2001):
P15 W9 D4 L1 GF32 GA14
P4 W2 D0 L2 GF7 GA4
P3 W3 D0 L0 GF9 GA1
P9 W6* D2 L2 GF13 GA6
P11 W9 D2 L0 GF23 GA6
P46 W31* D9 L6 GF86 GA32
*includes victories on penalties.