The Portuguese leaves the City Ground after just 21 months in charge - and only three games into the new season.
Nuno's position was always in doubt after criticising the club's summer market work and admitting his relationship with owner Evangelos Marinakis had deteriorated.
The 51-year-old took charge of Forest in December 2023 after the dismissal of Steve Cooper, guiding them to Premier League safety.
Last season Nuno led Forest to seventh in the Premier League - their highest finish since 1994-95 - as they qualified for the Europa League and Europe for the first time in three decades.
A Forest statement read this morning:
"Nottingham Forest Football Club confirms that, following recent circumstances, Nuno Espírito Santo has today been relieved of his duties as Head Coach.
"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.
"As someone who played a pivotal role in our success last season, he will always hold a special place in our journey."