Meanwhile, defending champions Manchester City host Fulham at the Etihad Stadium on Saturday.
London: Having already ended a 23-year wait for a league win at Old Trafford, Tottenham will aim for a first home victory against Manchester United in 12 years on Sunday.
Tottenham fans have to trace back to May 2001 to recall the last time Spurs beat United at White Hart Lane, when Willem Korsten scored twice in a 3-1 victory. They had to look back all the way to 1989 for an away victory, until Tottenham finally ended that streak with a 3-2 win at Old Trafford in September.
And with Andre Villas-Boas' team in good form, they have reason to hope for a home-and-away double. Spurs are unbeaten in their last six league matches, equaling their longest run without defeat under the Portuguese manager. The club has won seven and drawn one of its eight home matches in all competitions since a 1-0 loss to Wigan at White Hart Lane in early November.
Nevertheless, Villas-Boas is wary of a United side which sits top of the Premier League on 55 points, the club's highest-ever tally at this stage of a top-flight season. The 19-time English champions are unbeaten in their last 10 league games, and the former Chelsea manager does not think the September game will have an impact on Sunday's match.
"A lot of time has gone by in between," Villas-Boas said. "I think it was the fifth or sixth game of the season and United had already lost to Everton and lost to us at home. From then on they have been on a formidable run and they sit now with one more point than the league leaders last season who were Man City. The run of form is amazing. It is going to be a completely different game"
Spurs will be without influential midfielder Sandro for the visit of United, after the Brazil international was ruled out for the season with cruciate ligament damage in his right knee.
Sandro has had a key role in Tottenham's defensive midfield this season, but the Brazilian's long-term absence could see Scott Parker make his first Premier League start of the season. The England midfielder, a favorite under former Spurs manager Harry Redknapp, has not started a league game since April.
Tottenham also remain without defenders William Gallas (calf) and Younes Kaboul (knee), while Togolese striker Emmanuel Adebayor has left for the African Cup of Nations.
United have injury concerns of their own. Winger Ashley Young is out with a knee injury, while Jonny Evans has not recovered in time from a hamstring strain, so Rio Ferdinand and Nemanja Vidic will continue in central defense. Plenty of changes are anticipated following the midweek FA Cup win over West Ham, with the Premier League's top scorer Robin van Persie expected to return to the lineup.
The weekend's games include two London derbies, as Chelsea host Arsenal and Queens Park Rangers pay a visit to West Ham. Loic Remy is expected to make his QPR debut, after joining for a club-record fee on Wednesday. Club chairman Tony Fernandes sanctioned a move for the highly-rated France striker, as the Premier League's bottom side looks to avoid relegation from the top-flight.
Three points against West Ham could see QPR climb off the foot of the league table if Reading lose against Newcastle, in what has become a crucial match for both clubs. Newcastle are looking to end a run of seven losses in 10 matches in a bid to avert the ever-increasing threat of relegation.
Reading travel to Tyneside on the back of a morale-boosting 3-2 victory over West Bromwich Albion on Saturday. The Premier League strugglers staged one of the season's great comebacks, scoring three goals in the last 10 minutes to overturn the visitors' 2-0 lead.
The weekend's other fixtures include: Liverpool vs. Norwich; Manchester City vs. Fulham; Swansea vs. Stoke; Wigan vs. Sunderland; West Bromwich Albion vs. Aston Villa.
Monday's game sees Southampton host Everton, in what will be Mauricio Pochettino's first match in charge of the home side, following the sacking of former manager Nigel Adkins on Friday.