His departure marks the first managerial sacking in the English Premier League this season, News.Az reports, citing foreign media.
"The club thanks Nuno for his contribution during a very successful era," said a club statement released just after midnight.
The Portuguese had been in charge for 21 months at the City Ground, but two weeks ago said his relationship with the club's owner, the Greek billionaire Evangelos Marinakis, had deteriorated.
"Nottingham Forest Football Club confirms that, following recent circumstances, Nuno Espirito Santo has today been relieved of his duties as head coach," the club said.
The 51-year-old took charge in December 2023 after Steve Cooper was sacked and went on to save the club from relegation.
Last season the club finished seventh in the Premier League, their highest since 1994/95.
That secured a first European berth in 30 years, with a Europa League place handed to Forest instead of their initial Conference League spot, after Crystal Palace's demotion for breaching UEFA's multi-club ownership rules.
"The club thanks Nuno for his contribution during a very successful era at the City Ground, in particular his role in the 2024/25 season, which will forever be remembered fondly in the history of the club," said the statement
"As someone who played a pivotal role in our success last season, he will always hold a special place in our journey."
