At the end of the 1960s, the São Mamede Gallery opened its doors very close to Largo do Rato, on the street of the Polytechnic School, in a Pombalian building, almost opposite the General Procurator's Office of the Republic and the Church of São Mamede.

The gallery has been dedicated exclusively to modernity and the contemporary Portuguese movement, with temporary exhibitions of foreign artists. It has had an intense and quality artistic activity, supported by "classic" artists that were always linked to the Gallery, (such as Areal, Cesariny, Cruzeiro Seixas or Julio) but also, and above all, in new artists.

In 2005, it opened another headquarters in the city of Porto and in 2018 it expanded its facilities with the opening of a new space in Lisbon.