Jose Mourinho has left Manchester United with "immediate effect", the club has confirmed.
It comes after Manchester United's 3-1 defeat against Liverpool on Sunday.
The 55-year-old won three trophies during his first season at Old Trafford, but had come under increasing pressure this year with the team languishing in sixth place, 19 points behind their Merseyside rivals.
In recent months, the former Chelsea boss had fallen out with marquee signing and French World Cup winner Paul Pogba.
A statement from Manchester United on Tuesday read: "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 new caretaker manager will be appointed until the end of the current season, while the club conducts a thorough recruitment process for a new, full-time manager."
It is believed first-team coach Michael Carrick will take training on Tuesday and that a new caretaker manager will be appointed by the end of the week.
Mourinho had enjoyed considerable success at Porto, Chelsea, Inter Milan and Real Madrid before replacing Louis van Gaal at Old Trafford in 2016.
In his second season in charge, he guided United to second place in the Premier League behind rivals Manchester City.
And despite progression to the Champions League knockout stages this season, Mourinho had found himself under increasing pressure for his perceived style of negative football.
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Fallings-out with a number of his players was met with criticism from ex-pros such as Paul Scholes.
Mourinho's final game in charge came on Sunday, as league leaders Liverpool breezed past Manchester United 3-1 courtesy of goals from Sadio Mane and Xherdan Shaqiri.
In a move that summed up a turbulent few months at Old Trafford, Pogba, an £89.3 million signing, was an unused substitute for that match.
Self-titled the "Special One", Mourinho was the third manager to have taken the reins at Old Trafford since the departure of Sir Alex Ferguson in 2013.
United have not won the Premier League title since.
In his first season, the Portuguese won the Community Shield, EFL Cup and the Europa League.
But last season Manchester United ended the campaign trophy-less.
And United's haul of 26 points after their first 17 Premier League games this year is their worst start to a top-flight campaign since 1990-91.
Former Manchester United defender Gary Neville said he believed Tottenham Hotspur boss Mauricio Pochettino would be the "ideal candidate" for the vacant manager's role.
He told Sky Sports: "They need someone who meets the three key principals of that football club: the promotion of youth, entertaining football and to win football matches."
Neville said Mourinho was not the only person who needs to take responsibility for the club's fortunes.
"The players take responsibility, the board take responsibility, the manager and the coaching staff, obviously," he said.
Neville continued: "My personal view is that the club needs to reset.
"This is not just a moment to sack Jose Mourinho and appoint another manager, this is a moment for the club to take stock of what they're doing, to reset the structure in terms of recruitment, in terms of the decision making in the football club and make sure what they do next is the right move."
A number of names have already been cited as potential replacements.
Alongside Spurs boss Pochettino, ex-Real Madrid manager Zinedine Zidane has also been touted.
Didier Deschamps, who led France to World Cup glory both as a player and as a manager, and ex-Red Devils defender Laurent Blanc are also possibilities.
Former United first-team coach Rene Meulensteen said he could understand why the decision to part company with Mourinho was taken now.
The Dutchman, who worked under Sir Alex Ferguson at Old Trafford, told BBC Radio 5 live: "I think they've looked back critically to where they are and asked themselves, 'Is this the right way forward?', and with the transfer window right ahead of them, so I can understand the timing. "