Mourinho, who was sacked as Chelsea boss in December 2015, insists there is "nothing special at all" about the Premier League clash, claiming there is no extra emotion involved.
But the tie has served up plenty of dramatic moments down the years, and several with Mourinho in
The Blues can move seven points clear in the race for the Premier League title and edge ever-closer to rubber-stamping a second top flight crown in three season in the Chelsea dugout.
The Portuguese boss won his second straight title with a 3-0 win over Manchester United at Stamford Bridge, and the Blues can edge towards another crown at Old Trafford.
Antonio Conte's men will move seven points clear at the top with six games to play and move closer to rubber-stamping a second title in three seasons if they win at Old Trafford.
Below, Standard Sport takes a look at some of the more memorable previous encounters between the two sides
Dec 1905, Division Two: Man United 0 Chelsea 0
The first meeting between the two clubs attracted a remarkable crowd of 67,000 on Christmas Day in 1905. Played at United's then home of Venue Bank Street in Clayton, the game finished goalless. United would go on to finish second behind champions Bristol City and gain promotion, with Chelsea, in their first season in existence, nine points behind in third.
Jan 1998, FA Cup: Chelsea 3 Man United 5
Manchester United looked to be cruising to victory until the home side threatened a dramatic comeback. Two goals each from David Beckham and Andy Cole, and one for Teddy Sheringham, sent United into a 5-0 lead with 16 minutes remaining. But Chelsea rallied with goals from Graeme Le Saux and Gianluca Vialli, before Vialli's second three minutes from time set United's nerves jangling.
Apr 2006: Premier League: Chelsea 3 Man United 0
Mourinho's Chelsea guaranteed their second straight Premier League title with a 3-0 win at Stamford Bridge. William Gallas, Joe Cole and Ricardo Carvalho scored for the home side while the sight of Wayne Rooney being carried off on a stretcher sent the game into panic stations with the World Cup in Germany fast approaching.
May 2008: Champions League final: Man United 1 Chelsea 1 (6-5 pens)
United emerged successful from the first all-English Champions League final in Moscow. Cristiano Ronaldo opened the scoring for United before Frank Lampard equalised just before half-time. Didier Drogba was sent off in extra time and in a thrilling penalty shoot-out John Terry missed the chance to seal victory for Chelsea before Edwin van der Sar saved from Nicolas Anelka to seal United's win.
Oct 2016, Premier League: Chelsea 4 Man United 0
Mourinho clashed with Blues boss Antonio Conte and was serenaded with chants of "You're not special any more" as United crashed to an humiliating 4-0 defeat. Pedro opened the scoring after just 30 seconds and goals from Gary Cahill, Eden Hazard and N'Golo Kante contributed to Mourinho's miserable return.