The ex-United striker begins his temporary reign against another former club too, with Cardiff City - who were relegated under the Norwegian - welcoming the 20-time champions to South Wales.
For all of the change around the club this week, United are still a team in dire form, with their 3-1 defeat at Liverpool last weekend leaving them 19 points adrift of the leaders and closer to their struggling opponents than the leaders.
Here, Sports Mole looks at how Solskjaer could set his side out for this match.
A certain degree of guesswork has to go in to predicting Solskjaer's first XI, but he favoured a 4-3-3 system towards the end of his Molde stay and that formation would fit well with the players at his disposal at Old Trafford.
Mourinho's departure could act like a weight off the shoulders of many players, particularly Paul Pogba, who has struggled to get into the team of late but should return to the starting lineup under the new boss.
The match is likely to come too soon for Chris Smalling and Scott McTominay, while the likes of Marcus Rashford, Ander Herrera and Diogo Dalot could drop out of the side. Romelu Lukaku is expected to lead the line once again.