The teams occupy four of the top six positions in the table and none can afford to lose in their pursuit of either the title or a top-four finish and the prospect of Champions League football next season. (Agencies)
The other two places in the top six are filled by leaders Chelsea, who travel to Aston Villa, and Manchester City, who are at FA Cup semi-finalists Hull City.
A win for Chelsea on Saturday would lift them to 69 points and put them 10 clear of Liverpool and Arsenal who are not in action until Sunday.
Manchester City, who were knocked out of the Champions League by Barcelona on Wednesday, are nine points behind Chelsea with three matches in hand. Chelsea will have eight games left after this weekend, City 11.
Tottenham start the weekend in fifth place on 53 points with United sixth on 48 and with a game in hand on Spurs.
Judging by their entwined histories, more than a century of loathing between the fans, dramas and controversies - even before this season's earlier meetings are taken into account - events at White Hart Lane and Old Trafford are likely to overshadow everything else.
Both Spurs and Arsenal have plenty to prove in their third meeting of the season following Arsenal's 1-0 league win in September and their 2-0 victory in the FA Cup third round at the Emirates in January.
Arsenal were knocked out of the Champions League on Tuesday when they drew 1-1 at Bayern Munich but lost 3-1 on aggregate and they come to White Hart Lane without 42.1 million-pound ($70 million) record signing Mesut Ozil.
The German picked up a hamstring injury in Munich and according to manager Arsene Wenger will be out for several weeks, although he expects Aaron Ramsey to return for the first time since Boxing Day.
Arsenal reached the FA Cup semi-finals with a 4-1 victory over Everton last weekend and retain an outside chance of winning the title but their league form has dipped lately with just one win from their last four matches.
The teams occupy four of the top six positions in the table and none can afford to lose in their pursuit of either the title or a top-four finish and the prospect of Champions League football next season.