MASP distinguished itself by its involvement in several important initiatives concerning museology and art education in Brazil, as well as for its pioneering role as a cultural center.

[9] He intended to host the museum in Rio de Janeiro, but ultimately chose São Paulo, where he believed it would be easier to gather the necessary funds, since this city was enjoying a very prosperous moment.

[10] At the same time, the European art market had been deeply influenced by the end of World War II, making it possible to acquire fine artworks for reasonable prices.

In these first years of activity, the museum was located on the upper floors of the Diarios Associados headquarters in the Centro neighborhood of São Paulo.

The museum quickly became a meeting point for artists, students and intellectuals, attracted not only by its holdings, but also by the workshops and art courses it offered.

The courses were frequently given by important names of the Brazilian artistic scene, such as the painters Lasar Segall and Roberto Sambonet, the architects Gian Carlo Palanti and Lina Bo Bardi, the sculptor August Zamoyski, and the motion-picture technician Alberto Cavalcanti.

To preserve the required view of the downtown area, Bardi idealized a building suspended above ground, supported by four massive rectangular columns made of concrete.

Growing debts and the competition in the media market by Roberto Marinho's press conglomerate – caused the scarcity of the funds which had permitted the gathering of the collection.

In 1992, works of the French school and Brazilian landscapes were exhibited in the Museo Nacional de Bellas Artes, in Santiago, Chile, and in the Biblioteca Luís Angel Aragón, in Bogotá.

José Borges de Figueiredo, the investor who sold the plot of ground to the City Hall, wrote a non-binding letter to the administration, asking that it to be preserved as a "public place in perpetuity".

While in the following years multiple proposed projects ignored his wish, the architect Lina Bo Bardi and engineer José Carlos Figueiredo Ferraz ultimately conceived an underground block as well as a reinforced concrecte in tension suspended structure.

The building's installations and finishing are homely, as Lina Bo herself described: "Concrete visible, whitewash, a flagstone flooring covering the great Civic Hall, tempered glass, plastic walls.

In the museographic area, Lina Bo Bardi also innovated by using tempered crystal sheets leaned on concrete blocks bases as display supports for the paintings.

From 2013 to 2019 there was a negotiation of R$ 13 million with mobile telephone company Vivo to build a 125 m high observation tower, of architect Julio Neves, in the place, but they were unsuccessful.

Pietro Maria Bardi, formerly owner of commercial galleries in Milan and Rome, was in charge of searching and selecting the works which should be acquired, while Chateaubriand looked for donors and patrons, trying to tempt potential ones with banquets and lavish ceremonies.

Unlike other institutions, whose acquisitions depended on approval of a curators council, the São Paulo Museum of Art usually acquired its pieces quickly, sometimes by telegram.

Early modern French and Italian schools of painting are broadly represented, forming the main body of the collection, followed by Spanish, Portuguese, Flemish, Dutch, English and German masters.

On a smaller scale, the museum's holdings include representative objects of many periods and distinct non-Western civilizations – such as African and Asian arts – and others which stand out for their technological, archaeological, historic, and artistic relevance, like the select collections of Egyptian, Etruscan, Greek and Roman antiquities, besides other artifacts of Pre-Columbian cultures and medieval European art.

The museum faces controversy regarding five sculptures by Edgar Degas which are claimed by the family of Alfred Flechtheim who alleges they were stolen by the Nazis during World War II.

[21][22] On 20 December 2007, around 5:09 am, three men broke in to MASP and stole two paintings considered to be among the most valuable pieces in the museum's collection: O Lavrador de Café (The Coffee Farmer) by Cândido Portinari, and the Portrait of Suzanne Bloch by Pablo Picasso.

[25] Both pieces were recovered by the Brazilian police a few weeks after they were stolen, on 8 January 2008, in the city of Ferraz de Vasconcelos, in Greater São Paulo.

Just two months before the robbery, "two thieves tried to break into the museum but were spotted and fled",[24] and in 2005, MASP was forced to close temporarily "when its power was cut off for nonpayment of bills.