Together with German landscape architects Latz + Partner, and Spanish engineering consultants TYPSA, they will build an office complex that can house 5,250 people in the Belgian capital's European Quarter.
The consortium's design was chosen over nine other entries from international teams in a blind competition for the project.
"Future-proofed, resilient and innovative"
The European Commission complex will be built on the site of the current offices, and combine workspaces with public gardens, shops and an art gallery with the aim of improving the area for both employees and locals.
Compared to the existing buildings it will produce 50 per cent less carbon dioxide and use 70 per cent less energy to run.
"Major urban renewal projects are once in a generation opportunities to help places evolve," said Steven Charlton, managing director of the London studio of Perkins and Will.
"As a global practice with a strong London presence, we have worked extensively on many civic projects globally and believe that with technology and wellbeing far up the architectural agenda, there is a huge opportunity to drive forward new standards in sustainability and wellbeing."
European Commission runs the EU
The European Commission is the executive branch of the European Union, responsible for proposing legislation and running the EU on a day-to-day basis. The UK voted to leave the European Union in 2016, and is due to Brexit later this year.
The EU moved into a lantern-like headquarters designed by Samyn and Partners, Studio Valle and Buro Happold in 2017.
Perkins and Will was founded in 1935 by the late Lawrence Perkins and Philip Will in New York. Along with offices across the US and Canada, the firm has studios in London, Dubai, São Paulo and Shanghai. Recent sustainable designs from the practice include a plant-covered timber hybrid tower for Canada, and a house in Brazil with a green roof.