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The 55-year-old, appointed in May 2016, won the League Cup and Europa League in his first season in charge, but leaves the club after a dismal start to the season culminating in the 3-1 defeat at Liverpool on Sunday.
"Manchester United announces that manager Jose Mourinho has left the club with immediate effect,” a statement read.
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"We would like to thank him for his work during his time at Manchester United and 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."
Michael Carrick, who joined the club's coaching staff last summer following his retirement, will assume the role of interim manager.
The 37-year-old former England international will be assisted by Kieran McKenna until the club can appoint an external caretaker manager, a process that is expected to be completed within 48 hours.
In January this year, United handed Mourinho a contract extension until 2020 but currently sit sixth in the table, some 19 points behind league leaders Liverpool, and 11 points off Chelsea in fourth position - their haul of 26 points from 17 games represents the club's worst start to a season since 1990-91.
ODDS TO BECOME NEXT PERMANENT MANCHESTER UNITED MANAGER
Mauricio Pochettino 2/1
Zinedine Zidane 4/1
Laurent Blanc 5/1
Leonardo Jardim 9/1
Michael Carrick 10/1
Antonio Conte 12/1
Ryan Giggs 12/1
Arsene Wenger 20/1
Eddie Howe 20/1
Diego Simeone 20/1
THE TIMELINE OF MOURINHO’S DOWNFALL
United lose FA Cup final 1-0 to Chelsea, ending the season without a trophy for first time in three years.
Defeat in second game of new Premier League season 3-2 to Brighton & Hove Albion.
Mourinho sees his side lose 3-0 to Tottenham Hotspur at Old Trafford, the biggest home defeat of his career. Complains about 'respect' to media after the game.
Midfielder Paul Pogba says United should attack more at home after disappointing 1-1 draw with Wolves. Mourinho strips Frenchman of vice-captaincy in growing rift.
United dumped out of the League Cup at home by second-tier Derby County on penalties
3-1 defeat in the league by West Ham United means United suffer their worst start to a new season in 29 years.
Reported that Mourinho would be sacked as Manchester United regardless of the result against Newcastle United - United claimed a 3-2 win.
Comprehensively outplayed and beaten 3-1 by champions Manchester City away.
Another 3-1 defeat, this time by fierce rivals Liverpool which leaves United 19 points behind their league leading opposition.
Mourinho sacked with the club sixth in the Premier League.
MANCHESTER UNITED’S UPCOMING FIXTURES
- Cardiff City (a), 22nd December, Premier League
- Huddersfield Town (h), 26th December, Premier League
- AFC Bournemouth (h), 30th December, Premier League
- Newcastle United (a), 2nd January, Premier League
- Reading, 5th January (h), The FA Cup
- Tottenham Hotspur (a), 13th January, Premier League
- Brighton & Hove Albion (h), 19th January, Premier League
- Burnley (h), 29th January, Premier League
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