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The dismissal of the Portuguese follows growing tensions between Amorim and the Old Trafford hierarchy, including director of football Jason Wilcox, in recent days.
The club, sixth in the Premier League after a 1-1 draw at Leeds on Sunday, issued a statement saying Amorim had "departed his role as head coach of Manchester United".
"With Manchester United sitting sixth in the Premier League, the club's leadership has reluctantly made the decision that it is the right time to make a change," the club said.
"This will give the team the best opportunity of the highest possible Premier League finish.
"The club would like to thank Ruben for his contribution to the club and wishes him well for the future."
Current under-18s coach Darren Fletcher will take charge of the team against struggling Burnley on Wednesday.