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Sir Alex Ferguson's side have already won the Club World Cup and lifted the League Cup against Tottenham at Wembley on Sunday, making the dream of winning every competition they have entered an increasingly distinct possibility.
While Ferguson continues to play down United's chances of sweeping the board, the Scot will know only too well that the next seven days could put his team in an even stronger position.
A victory at St James' Park could open up a 10-point lead if Chelsea, in second place, and Liverpool, in third, come unstuck in their matches on Tuesday against Portsmouth and Sunderland respectively.
After their trip to Newcastle, United face Fulham in the FA Cup quarter-finals on Saturday, then host Inter Milan in the Champions League last 16 second leg next week.
United, who are on a 15-match unbeaten run, have won five of their last six visits to St James' Park, scoring 20 goals in the process.
Ferguson is likely to bring back Michael Carrick, Dimitar Berbatov and Nemanja Vidic after all three were left out of Sunday's starting line-up, while Wayne Rooney could recover from a virus.
Rio Ferdinand, who captained United at Wembley, warned his team-mates they still have room for improvement despite their remarkable winning run.
"The momentum is with us but there are still loads of improvements to make," he said.
"We did well in parts against Tottenham but they managed to get through to our back line too easily on occasion so we need to cut that out.
"It is down to us really. If we win the rest of our games, obviously we will be champions and the way the results have panned out has been quite good.
"But it is not over. We still know Chelsea and Liverpool can go on unbeaten runs until the end of the season. We have to make sure we do as well as them."
Elsewhere on Wednesday, Aston Villa will attempt to consolidate their place in the top four at inconsistent Manchester City.
Villa have stumbled in recent weeks and were forced to settle for a 2-2 draw against Stoke on Sunday after blowing a two-goal lead in the final minutes.
But Norway striker John Carew expects Villa to bounce back and register their eight successive away league win this season at Eastlands.
"We have a great chance as there is still a gap between ourselves and Arsenal," he said.
"We were sad for an hour after the Stoke game but then you look forward to the next challenge - and be confident that you can be successful.
"This team has done great things away from home this season and there is no reason why we cannot do it again."
Tottenham must recover quickly from the agony of losing the League Cup final shoot-out as they host fellow strugglers Middlesbrough.
Harry Redknapp's team are only two points ahead of Middlesbrough, who currently fill the final relegation position, and midfielder Jermaine Jenas said: "We can take a lot out of the final, there was a lot of courage and effort, and if we put that in from now until the end of the season then we'll climb the league.
"We haven't got time to think about it. We have a very important game on Wednesday that we have to focus on and make sure we are ready."
