United were imperious in a 4-0 thrashing of Sunderland on Wednesday to move a point above Arsenal, who could be four adrift by the time they begin their match at Everton later in the day.
Third-placed Chelsea know they can ill afford many more dropped points as they host Newcastle United while Liverpool and Manchester City battle for fourth place on Sunday.
United were beaten home and away by West Ham last year despite the Hammers spending most of the season in the relegation zone and Ferguson has suffered several disappointments against them in the past.
Carlos Tevez, the man who inspired West Ham to a remarkable escape from the drop last season, including a final-day winner at Old Trafford, will no doubt get a warm welcome from the Upton Park faithful.
Tevez has now become a favourite at Manchester United since his move north and has struck up a lethal combination with Wayne Rooney. After being rested against Sunderland, the Argentine will be raring to go in the second of United's holiday fixtures.
MID-SEASON DIP
Arsenal have looked vulnerable in recent weeks. A defeat at Middlesbrough was followed by a fortunate 2-1 victory over Tottenham and a Boxing Day stalemate at Portsmouth.
With several players, notably Kolo Toure, heading off to the African Nations Cup next month, manager Arsene Wenger will be worried about a mid-season dip in form.
Sixth-placed Everton have been in tremendous form of late with last weekend's defeat by Manchester United a rare blip. They hit back with a 2-0 victory over Bolton on Wednesday and will be relishing getting their teeth stuck into Arsenal.
Last season, Chelsea's form over Christmas which resulted in three draws, de-railed their title defence and coach Avram Grant's hopes of winning the Premier League in his first season will be fading fast if the Londoners do not beat Newcastle.
Quite who will be playing for the Blues in another matter. Frank Lampard and Andriy Shevchenko limped out of their amazing 4-4 draw with Aston Villa to join John Terry, Didier Drogba, Claude Makelele and Florent Malouda on the injured list.
With Ricardo Carvalho suspended and possibly Ashley Cole too after their red cards against Villa, even Chelsea's glittering resources are looking a little threadbare.
(Reporting by Martyn Herman; Editing by John O'Brien)