Second hosts third at Old Trafford with only goal difference separating United from Mauricio Pochettino's side in the game of the weekend.
The visitors have suffered a major injury blow as star man and talismanic striker Harry Kane will miss the trip to Old Trafford with a hamstring strain.
In contrast, United are boosted by the return of Ivorian centre-back Eric Bailly, who is set to feature having not played since the end of September through injury.
Phil Jones is also available, and Marcos Rojo is also nearing full fitness, but midfielders Paul Pogba, Marouane Fellaini and Michael Carrick all remain sidelined.
Despite their Carabao Cup defeat to West Ham on Wednesday, when a 2-0 lead turned into a 3-2 defeat, Spurs again look well equipped to fight it out at the top of the Premier League once more.
They swept aside Jurgen Klopp's Liverpool with a hugely impressive 4-1 victory at Wembley last time out for a fourth successive league win (Kane scored twice, added to by strikes from Dele Alli and Son Heung - min).
United manager Jose Mourinho issued a rallying cry for the fans to make the Old Trafford atmosphere one to remember.
He said: "We had very good atmospheres against Liverpool and Chelsea, so if the supporters can make the stadium very loud again then it is a positive for us.
"Normally at home we are a strong and confident team and we look to do the same on Saturday, Spurs are a very good team and one of the best in the league.
"They have a fantastic squad, a very good manager, stability and years with him (Pochettino), the same players.
"They are a really, really, really good side but I think we are fine, we are strong and I think we are ready."
Even ten games into the season, this looks a clash of huge significance with the Reds having faltered a little since the international break
Last week's defeat to Huddersfield saw unbeaten City open up a five point lead at the top, with our next two opponents - Tottenham and Chelsea, now right on the Reds coattails.
The two sides sit locked together in the table level on points, with United's superior goal difference the only advantage.
United go into the game having won five on the bounce at home without conceding a goal, while Spurs boast a 100% record on the road - so something has to give at Old Trafford.
Form guide: United W W D W L W Tottenham W W W D W L
Match odds: United 6/5 Draw 12/5 Tottenham 11/4
Referee: Jon Moss (West Yorkshire)