United slipped to a 1-0 defeat at Arsenal, setting up a virtual title decider with Chelsea next Sunday at Old Trafford.
Aaron Ramsey, who chose to join the North Londoners ahead of the Reds, scored the only goal of the game to inflict a fourth defeat of the Barclays Premier League campaign on the leaders.
Substitute Michael Owen was denied a late penalty when being brought down inside the box with a couple of minutes remaining after Nemanja Vidic appeared to escape conceding a spot-kick for a handball in the first half.
But the Reds were not at their best and rarely replicated the sort of form displayed against Schalke in midweek.
Sir Alex Ferguson opted for Fabio at right-back and Nani in preference to Antonio Valencia with Anderson drafted into the midfield while the Gunners were without Cesc Fabregas, who injured a thigh in training.
Even without their captain, the hosts started brightly in the sunshine and dominated early possession - although Edwin van der Sar wasn't called into action.
Jack Wilshere lashed a great opportunity wide after a rare slip by Vidic, who cleared straight to the young Englishman, but the Reds' skipper was at his best to pressure Theo Walcott into firing a Robin van Persie cross over the bar soon afterwards.
Patrice Evra was on the top of his game to stretch to divert a van Persie centre away from Walcott and it took some time for United to fashion a threatening move. When it came, Fabio burst onto a Nani pass and stayed on his feet despite a risky challenge inside the box, only to be unable to pick out Javier Hernandez in the middle.
There was a nervous moment on 32 minutes when Vidic appeared to get a feint touch with his fingertips to a Walcott cross with van Persie lurking behind him. Only the Dutchman really appealed but, no doubt, it was a talking point and it did seem to be a moment of madness from Vidic.
Aaron Ramsey and Wayne Rooney traded off-target shots before the Reds striker was harshly booked by Chris Foy for a nudge on Wilshere. Wojciech Szczesny was finally brought into action before half time when gathering Anderson's tame attempt following a more encouraging move which involved Nani and Evra.
United carried more threat after the break with Rooney forcing a save out of Szczesny with a free-kick and Evra ramming the rebound into the side-netting while Nani delivered a great cross that just evaded Hernandez before sending his own set-piece effort bouncing wide.
But Arsenal broke through on 56 minutes, seconds after Antonio Valencia replaced Anderson in midfield and the players were still reorganising.
Wilshere fed van Persie on the right and the striker was afforded too much time to pick out the unmarked Ramsey, who guided his shot past van der Sar's right hand and into the corner of the net.
United needed to muster a response and Vidic headed wide from a Nani corner before the manager replaced Hernandez with the league's top goalscorer Dimitar Berbatov.
The visitors finally started building up a head of steam as Ramsey handled a Michael Carrick cross on the edge of the box, arguably inside, but Rooney's free-kick was comfortable for Szczesny.
Rooney did well to find Nani during one smart break but the Portuguese winger's shot was beaten out by Szczesny, although the Gunners still looked dangerous themselves with van Persie a constant threat.
Owen joined the Reds' attack, in place of Carrick, but was denied what looked a blatant penalty with a couple of minutes left when turning Clichy inside the area. Referee Foy waved away the appeals and there was to be no late drama with the team needing to pick themselves up for two huge games in the coming week.