The Grassi family sold the palazzo in 1840, with ownership that followed passing through many different individuals. In 1857, the building was bought by Baron Simeone De Sina. A small scenic garden was created adjacent to the building.

In 1951, the building became the International Centre of Arts and Costume. The adjacent garden was turned into an open-air theatre (Teatrino), which was finally covered in the 1960s. The International Centre for Arts and Costume closed in 1983. The Palazzo was purchased by the Fiat Group in 1983, under the late chairman Gianni Agnelli, and it underwent a complete restoration overseen by architect Gae Aulenti. The group's aim was to transform Palazzo Grassi into an exhibition hall for the visual arts. It continues to be used as an art gallery today. Between 1984 and 1990, Pontus Hultén was in charge of the art museum which also contained a 600-seat outdoor theatre. In 1990, the architect Aldo Rossi received the Pritzker Architecture Prize in this building.

In May 2005, the French entrepreneur François Pinault bought the Palazzo Grassi for 29 million euros. The remodeling of the building was assigned to the Japanese architect Tadao Ando. The Palazzo reopened in April 2006 with the exhibit Where Are We Going?. The Palazzo is divided in 40 rooms, providing 5,000 m2 of exhibition floor. Jean-Jacques Aillagon was the museum's first director. In 2007, François Pinault acquired the Punta della Dogana to transform it into a contemporary art museum paired with the Palazzo Grassi. The replanning of the building, which was in disrepair when acquired, was also assigned to Tadao Ando.[8] The Punta della Dogana reopened after 14 months of renovation. In 2013, Tadao Ando redesigned the Teatrino into a 225-seat auditorium.