Antonio Conte's men comprehensively beat United 4-0 in the Premier League in October - a game that marked Mourinho's first return to Stamford Bridge since being sacked by Chelsea - before the Blues knocked the Red Devils out of the FA Cup quarter-finals with a 1-0 home win in March.
But Chelsea will now have to go to Old Trafford - where United have drawn nine times in the top flight this season - as they attempt to keep in tact their seven-point lead over Tottenham.
The task will be made more difficult by the fact that United are unbeaten in 21 league matches, while the heat could be on Chelsea given title rivals Spurs play a day earlier.
Standard Sport previews the big clash below...
United play Chelsea on Sunday 16 April at Old Trafford. The game kicks off at 4pm.
TV AND ONLINE COVERAGE
The match will be shown live on Sky Sports 1 from 3.30pm. Alternatively, you can follow all the build-up and action from 3.30pm with Standard Sport’s live blog.
Can't see the live blog? Click here for the desktop version.
David De Gea is set to return to the Manchester United's starting line-up after missing last weekend's trip to Sunderland with a minor injury and was an unused substitute in the midweek trip to Anderlecht.
Wayne Rooney (ankle) and Ashley Young (groin) trained before that match so will be hoping to prove themselves fit for Sunday, but Phil Jones (foot), Chris Smalling (knee) and Juan Mata (groin) are out.
Provisional squad: De Gea, Romero, Pereira, Valencia, Blind, Darmian, Shaw, Rojo, Tuanzebe, Fosu-Mensah, Bailly, Mkhitaryan, Carrick, Herrera, Young, Lingard, Pogba, Fellaini, Rooney, Martial, Rashford, Ibrahimovic
Chelsea goalkeeper Thibaut Courtois has been ruled out of the trip to Old Trafford.
The Stamford Bridge No.1 suffered an ankle injury in training, with back-up keeper Asmir Begovic set to take his place.
Wing-back Victor Moses returned from a toe injury against Bournemouth last Saturday and came through unscathed.
Provisional squad: Begovic, Eduardo, Fabregas, Zouma, Alonso, Kante, Hazard, Loftus-Cheek, Moses, Pedro, Costa, Matic, Willian, Batshuayi, Cahill, Terry, Azpilicueta, Chalobah, Luiz, Eduardo, Aina, Ake.
Manchester United starting XI: Romero, Darmian, Bailly, Rojo, Shaw, Fellaini, Herrera, Pogba, Mkhitaryan, Ibrahimovic, Lingard.
Chelsea starting XI: Courtois, Azpilicueta, Luiz, Cahill, Moses, Kante, Matic, Alonso, Pedro, Costa, Hazard.
BETTING ODDS (via 888Sport)
- Manchester United to win: 9/5
- Chelsea to win: 7/4
- Draw: 43/20
Click here to place a bet. Odds correct as of April 16 at 10am.