The core mission of the museum is to present the personal collection of Peggy Guggenheim. The collection holds major works of Cubism, Futurism, Metaphysical painting, European abstraction, avant-garde sculpture, Surrealism, and American Abstract Expressionism, by some of the greatest artists of the 20th century. These include Picasso (The Poet, On the Beach), Braque (The Clarinet), Duchamp (Sad Young Man on a Train), Léger, Brancusi (Maiastra, Bird in Space), Severini (Sea=Dancer), Picabia (Very Rare Picture on Earth), de Chirico (The Red Tower, The Nostalgia of the Poet), Mondrian (Composition No. 1 with Grey and Red 1938 / Composition with Red 1939), Kandinsky (Landscape with Red Spots, No. 2, White Cross), Miró (Seated Woman II), Giacometti Woman with Her Throat Cut, Woman Walking), Klee (Magic Garden), Ernst (The Kiss, Attirement of the Bride), Magritte (Empire of Light), Dalí (Birth of Liquid Desires), Pollock (The Moon Woman, Alchemy), Gorky (Untitled), Calder (Arc of Petals) and Marini (Angel of the City).

The museum also exhibits works of art given to the Solomon R. Guggenheim Foundation for its Venetian museum since Peggy Guggenheim's death, as well as long-term loans from private collections. From July 1997 to September 2015, the Peggy Guggenheim Collection exhibited a selection of 26 masterpieces from the world-renowned Mattioli Collection of early 20th-century Italian art, including important works by Giacomo Balla, Umberto Boccioni, Carlo Carrà, Fortunato Depero, Amedeo Modigliani, Giorgio Morandi, Ottone Rosai, Luigi Russolo, Gino Severini, Mario Sironi, and Ardengo Soffici.

Hannelore B. and Rudolph B. Schulhof Collection
In October 2012 eighty works of Italian, European and American art of the decades after 1945 were added to the collections of the Solomon R. Guggenheim Foundation in Venice. They were the bequest of Hannelore B. Schulhof, who collected the works with her late husband Rudolph B. Schulhof. They include paintings by Burri, Dubuffet, Fontana, Hofmann, Kelly, Kiefer, Noland, Rothko, and Twombly, as well as sculptures by Calder, Caro, Holzer, Judd and Hepworth. The Hannelore B. and Rudolph B. Schulhof Garden exhibits works from this collection.

Patsy R. and Raymond D. Nasher Sculpture Garden
The Patsy R. and Raymond D. Nasher Sculpture Garden and other outdoor spaces at the Peggy Guggenheim Collection presents works from the permanent collections and Foundation (by Arp, Duchamp-Villon, Ernst, Flanagan, Giacometti, Gilardi, Goldsworthy, Holzer, Marini, Minguzzi, Mirko, Merz, Moore, Ono, Paladino, Richier, Takis), as well as sculptures on temporary loan from foundations and private collections (by Calder, Kapoor , Marini, Nannucci, Smith).