The Dutchman oversaw three wins and a draw in interim charge after the sacking of Erik ten Hag but will not be part of the new era at Old Trafford.
Van Nistelrooy returned to the club in the summer to work under Ten Hag, having left Old Trafford 18 years ago. He had suggested a willingness to stay under Amorim and see out the 18 months on his deal. United also confirmed the exit of fellow coaches Rene Hake, Jelle ten Rouwelaar and Pieter Morel.
United said: "Ruud is, and always will be, a Manchester United legend. We are grateful for his contribution and the way in which he has approached his role throughout his time with the club. He will always be very welcome at Old Trafford."
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