The Portuguese manager has been at the club for four years and in that time he earned the Wanderers promotion to the Premier League, in his first season.
The following campaign a seventh-placed finish granted the club qualification into the Europa League, a competition in which Wolves reached the quarter-finals of.
However, after a disappointing 2020/21 campaign that sees them sit 12th in the top-flight, the club have decided to part companies with Nuno by mutual consent.
"We achieved our goals"
Upon the announcement of Santo's departure, he said: "Since the first day we arrived at Compton, our ambition was to make a positive change and push this football club forward, and I am proud to say that we did that every single day.
"We achieved our goals, we did it with passion and we did it together.
“Firstly, I want to thank the supporters, who have all played such an important part in helping us reach new heights for Wolves, and the people of the city, who embraced us and made us feel at home.
“I, of course, want to thank all of the staff at Wolves, for their support and total commitment, every single day."
The 47-year old added: "Most importantly, I want to thank each-and-every player that we’ve worked with since the day we started, for their loyalty, their dedication, hard work and talent.
"They are the ones who have made this amazing journey possible for us.
"Sunday will be a very emotional day, but I am so happy that the fans will be back in Molineux and we can share one last special moment together, as one pack.”
"We cannot thank him enough for the progress he has made"
When speaking on the announcement executive chairman Jeff Shi said: “Nuno has brought us some incredibly special moments at Wolves that will never be forgotten, but every chapter comes to an end.
"His loyalty and dedication over the last four years has been immeasurable, and we cannot thank him enough for the progress he has made for Wolves.
“Sunday was already going to be a very special day, welcoming our supporters back for the first time in more than a year; but it will also now be a fitting goodbye for someone who will forever remain an important part of Wolves history.”