Nuno’s Spurs had recorded five wins and five losses in the Premier League this term, sitting ninth on the table, while they have only managed four points from three games in the UEFA Conference League.
The final straw was Saturday’s Premier League defeat to the Red Devils, who were under pressure themselves after a woeful 5-0 home loss to Liverpool which followed a 4-2 loss to Leicester City.
Former Chelsea and Inter boss Antonio Conte has been linked as the early favourite to replace Nuno, having reportedly flown into London on Monday.
Tottenham managing director Fabio Paratici said on Monday: “I know how much Nuno and his coaching staff wanted to succeed and I regret that we have had to take this decision.
“Nuno is a true gentleman and will always be welcome here. We should like to thank him and his coaching staff and wish them well for the future.”
The club added in its statement: “A further coaching update will follow in due course.”
Nuno had followed Jose Mourinho at Tottenham, with the Portuguese only lasting 18 months in the role.
Mauricio Pochettino, now manager at Paris Saint-Germain, had been in the position from 2014 to 2019, guiding Spurs to the 2019 UEFA Champions League final and regular qualification for Europe’s top competition.
Among the other reported candidates for the Spurs job are Porto boss Sergio Conceicao, ex-Roma head coach Paulo Fonseca and Ajax manager Erik ten Hag.