The distance between two of their fiercest rivals, the style of play and increasing friction between Mourinho and United's star signings forced the board to act.
"The club would like to thank Jose for his work during his time at Manchester United and to wish him success in the future," a club statement said.
Mourinho rolled into Old Trafford in the summer of 2016 after six months out of the game following his departure from Chelsea in December 2015. His dismissal came seven months after leading the west Londoners to the 2015 Premier League title.
There were many who questioned whether Mourinho's defensive ethos would fit in and prosper at a club where the faithful are weaned on attacking exuberance.
But he started with victory. United, as winners of the FA Cup, claimed the pre-season curtain raiser the Community Shield. They beat the Premier League champions Leicester City 2-1.
They eventually finished the 2016/2017 season in sixth place 24 points behind the champions Chelsea. But at least the League Cup and the Europa League were glittering vindications of his tenure.
The 2018 season witnessed an improvement in United's Premier League fortunes.
They finished second with 81 points. But it was light years behind Manchester City who clocked up a Premier League record of 100 points and a plethora of plaudits for their 106 goals in 38 games.
The 2018/2019 season has been a slough of despond for the United faithful. They have made their worst start in 28 years and 55-year-old Mourinho has already excused them from the race for the 2019 title.
"A caretaker-manager will be appointed until the end of the season while the club conducts a thorough recruitment process for a new, full-time manager," the club statement added.
The frenzy will commence as to the identity of that manager. Zinedine Zidane, who led Real Madrid to three consecutive Champions League crowns, will be among the men in demand.
Massimo Allegri, the Juventus manager will also be a contender after winning titles in Serie A with AC Milan and Juventus.