Van Gaal said he was "very disappointed" to be sacked on Monday just 48 hours after leading United to victory in the FA Cup final against Crystal Palace.
Missing out on a lucrative Champions League place proved the final straw for the club's United States-based owners, the Glazer family, and they didn't let United's first piece of silverware since the 2013 retirement of legendary boss Alex Ferguson stop them from wielding the axe.
With van Gaal having cleared out his desk at United's Carrington training ground after talks over a settlement for the final year of his three-year contract, which had been worth a reported £6.4 million per year ($9.2 million, 8.2 million euros), the path is clear for former Chelsea manager Mourinho to be confirmed as the new United boss on Tuesday.
Mourinho was sacked by Chelsea in December after a miserable campaign marred by a series of rifts with the club's star players that eventually became intolerable to owner Roman Abramovich as the team, champions just months earlier, languished near the relegation zone.
Now the 53-year-old will hope to restore his reputation by restoring the sparkle to United's own tarnished image.
Mourinho's agent Jorge Mendes is said to be arriving in Manchester on Tuesday to tie up a deal that has been widely reported in the British media, setting the stage for one of the sport's most intriguing characters to at last manage United after a glittering career that so far features 21 major trophies, including three Premier League crowns and two Champions League titles.
Former United goalkeeper Peter Schmeichel believes Mourinho is the right man to get the club back on track.
"On the top of Mourinho's list was always Manchester United, now he has the opportunity," Schmeichel told the BBC.
"Now they have a guy that is supposed to be the biggest manager in the world, the one that really could save
"It has been a brave decision but one that is long overdue."
From the moment, Mourinho danced a jubilant jig down the Old Trafford touchline after a late goal from Costinha gave his Porto side the draw they needed to eliminate Alex Ferguson's men from the 2004 Champions League, the colourful and controversial Portuguese has seemed destined to manage United.
He thought his time had come when Ferguson retired, but concerns over his volatile nature prompted United to turn to the more conservative David Moyes instead.
But with that move proving a disaster and van Gaal faring little better, United's powerbrokers have decided to take a chance on Mourinho.
Pictured strolling with his former Chelsea assistant Rui Faria while removal men took boxes away from his London home on Monday, Mourinho appeared the picture of contentment.
But he is a far less convivial figure once the battle lines are drawn, both with opponents and even his own players.
Having famously locked horns with the likes of Arsene Wenger and Rafael Benitez during his two spells with Chelsea, Mourinho will arrive at United just in time to resume hostilities with Pep Guardiola, who is about to leave Bayern Munich for his first taste of the Premier League as Manchester City boss.
Mourinho, then in charge of Real Madrid, never wasted a chance to take a swipe at Barcelona manager Guardiola during their time in Spain.
But it was Guardiola who had the better of it, with Mourinho winning just three of their 16 meetings.
The duo will go head-to-head for the first time when United face City in the pre-season International Champions Cup in Beijing on July 25.
By then, Mourinho will hope to have significantly improved an unbalanced and often lacklustre United squad.
Paris Saint Germain forward Zlatan Ibrahimovic, Sporting Lisbon midfielder Joao Mario, Everton defender John Stones, Chelsea midfielder Nemanja Matic and Atletico Madrid forward Antoine Griezmann are reportedly among the names on his wanted list.
But Mourinho, expected to bring Faria and goalkeeping coach Silvino Louro with him to Old Trafford, might also have to deal with scepticism from the United squad after a report that some senior players have already expressed concern the tactically conversative coach might prove too similar to van Gaal.
Van Gaal's dull tactics frustrated United fans, while the players were reportedly infuriated by his habit of staging
video review sessions in which he would criticise their mistakes in front of the team.
If he can rebuild the confidence of his squad and make United champions for the first time since 2013, Mourinho may regard it as his finest achievement yet.