The scene is set for the first of two monumental clashes in the space of a week for the Reds as we travel to an Arsenal side who have won their last 12 at home in all competitions.
United host runaway unbeaten leaders City at Old Trafford next weekend but first must negotiate the always difficult challenge posed by the in-form Gunners, who haven't lost at the Emirates since March. That run included a 2-0 win over United in May, which saw Arsene Wenger finally get one over on his arch-enemy Jose for the first time in a competitive match.
The boss has a score to settle against his bitter rival as the two men - who famously despise each other - locks horns again in the latest chapter of their storied and long-running feud.
This is a fixture that used to be the most eagerly anticipated match on the calendar but, although the fierce loathing between the clubs has subsided significantly in recent years, it's still a meeting of two of the country's biggest and most successful clubs.
Both teams are set to be without key men for this Saturday tea-time kick-off, as United once again look to move to within five points of City, at least until Pep Guardiola's side host struggling West Ham on Sunday.
Arsenal, meanwhile, could go third with a victory that would put them one point behind us, in an increasingly congested tussle at the top of the table.
Their hopes have been hit, however, by the absence of top scorer Alexandre Lacazette who went off with a groin injury in their midweek thrashing of Huddersfield and is definitely out.
Alexis Sanchez is expected to be fit despite a minor hamstring issue, with Olivier Giroud set to come in for Lacazette as the focal point in attack.
Nemanja Matic (muscular) and Marouane Fellaini (knee) are both doubtful, although Matic has travelled to London with the squad despite limping off in the win against Watford. It remains to be seen whether the Serbian - who has been ever present in the league so far - will be deemed fit enough to feature.
Michael Carrick will be available again soon after a heart procedure, but Eric Bailly and Phil Jones are both out. In form Victor Lindelof looks set to keep his place, therefore, as Jose ponders whether to keep the three at the back system he used to good effect at Vicarage Road.
The boss said: "I remember even before I came to England in 2004, it was always about Manchester United and Arsenal for the title. It's not like that now always, but it is still an important match for the fans and for the players as Arsenal is a difficult opponent.
"We will attack with 11 players when we have the ball, because even the goalkeeper needs to know what to do in that situation. When Arsenal have the ball, we will defend with 11 players.
"It is something that is said a lot, but I do it, I play a game at a time and don't think far ahead. I always tell my players to think about the one game, I always say this as you have to stay focused."
Form guide: Arsenal D L W L W W United W L W L W W
Match odds: Arsenal 6/4 Draw 12/5 United 11/5
Referee: Andre Marriner.