The Dutchman had been at Goodison Park since the summer of 2018 and was involved in the Toffees spending close to £300million during that period.
It failed to translate into on-field success, however, and with Everton struggling this season, Brands was relieved of his duties.
“Everton Football Club can confirm that Marcel Brands has left his post as director of football,” a club statement read.
“The owner and directors would like to thank Marcel for the service he has given to the club over the past three-and-a-half years and wish him well for his future.
“A strategic review of the football structure will now take place which will inform the best model for the club to proceed with in the long-term.
“In the meantime, the owner and board of directors will continue to provide our manager, Rafa Benitez with their full support.”
Brands only signed a new three-year deal in April but poor recruitment in the past saw Benitez able to spend just £1.7million this summer, with financial fair play restrictions hitting the Merseyside outfit hard.
After a strong start to the campaign, Everton’s form has nosedived due to a mixture of injuries and a lack of suitable options with the Toffees’ midweek defeat to Liverpool sparking angry scenes at Goodison Park.
Supporters turned their frustration on the board and in particular Brands after the 4-1 loss with the 59-year-old now bringing his tenure to an end due to a “clear difference” in the vision and direction of the club.
In a statement, he said: “On Friday, following a personal conversation with the chairman and my fellow board members, we agreed that I would step down from my post as director of football and as a member of the Everton Football Club Board.
“This decision has taken some time and some consideration and was one of the most difficult I have faced in my career.
“The board and I agreed that there is a clear difference in the vision and direction for this beautiful club and, with that in mind, the decision was taken.
“I want to thank everyone in the club who I have worked closely with over the last three and a half years. There are a lot of talented people at Everton with huge passion and commitment to move the club forward, both on and off the pitch.
“I want to wish all of the squad every success, and I am convinced that there is enough quality to improve the current situation quickly.
“It has been an honour for me to work at this fantastic club and I wish everyone associated with Everton the very best for the future.”