The office's best-known buildings include the GSW Headquarters in Berlin, the Federal Environment Agency in Dessau and the Brandhorst Museum in Munich.

[1] Early competition entries for Paternoster Square in London (1989), Tokyo International Forum (1989) and the Junction Building in Birmingham (1989) all offered socio-culturally and environmentally sustainable alternatives to the conventions in architecture and planning at the time.

[citation needed] The winning competition proposal by Sauerbruch Hutton was a critique of the "Critical reconstruction" established by Hans Stimmann, Berlin's building director from 1991 to 2006.

In 2008, with the Brandhorst Museum, Sauerbruch Hutton also began exploring the applications of glazed ceramic as a facade material which is being continued in the development of the M9 Museum in Mestre/Venice.The firm's GSW Headquarters won the Berliner Architekturpreis and Deutscher Architekturpreis, as well as several RIBA and AIA Awards and was nominated for a Stirling Prize in 2000.

He has worked at Rem Koolhaas's Office for Metropolitan Architecture in London, leading the House at Checkpoint Charlie project.

He has maintained an involvement in teaching throughout his professional career, having held professorships at the University of Virginia, the State Academy of Art and Design in Stuttgart and Technische Universität Berlin.

He's a commissioner of the Zurich Building Council, a trustee of the Bauhaus Dessau Foundation and a Honorary Fellow of the American Institute of Architects.

Since 2023 the responsibilities for the office are shared by 16 partners and 10 associates, with Matthias Sauerbruch, Juan Lucas Young, Vera Hartmann and David Wegener as directors.