By 1949, the elaborate cast concrete ornamentation of the original de Young was determined to be a hazard and removed because the salt air from the Pacific had rusted the supporting steel.

[4] When the structure was demolished and replaced by a new building, which opened in 2005, the only remaining original elements of the old de Young were the vases and sphinxes located near the Pool of Enchantment.

Although the permanent collection is national in scope, art made in California from the Gold Rush era to the present day is also on display in the de Young.

The permanent collection galleries integrate decorative arts objects with paintings and sculptures, emphasizing the artistic, social, and political context for the works on display.

ARTnews reported that the gift included works by well-known American artists like Georgia O’Keeffe, Winslow Homer, John Singer Sargent, Charles Sheeler, and Alexander Calder.

Contemporary acquisitions include Wall of Light Horizon (2005), by Sean Scully and signature sculptures by Zhan Wang and Cornelia Parker.

The strength of the collection lies in artists associated with California, including Piotr Abraszewski, Christopher Brown, Squeak Carnwath, Jim Christensen, Robert Colescott, Hung Liu, Bruce Nauman, Rachel Neubauer, Ed Ruscha and Masami Teraoka.

Lens-based and time-based media works include those by Nigel Poor, Catherine Wagner, Rebeca Bollinger, Alan Rath, the Propeller Group, Firelei Baez, Carrie Mae Weems, and Lisa Reihana.

The museums have also acquired works by artists such as Anish Kapoor, Odd Nerdrum, Gottfried Helnwein, Doris Salcedo, David Nash, Rose B. Simpson, Barbara Hepworth, Richard Deacon, and Frank Bowling.

With a $1 million grant from the Svane Family Foundation, in 2023 the Fine Arts Museums acquired works by 30 Bay Area artists, including Wesaam Al-Badry, Rupy C. Tut, Woody D. Othello, and Chelsea Ryoko Wong.

[9] The exhibition Crafting Radicality: Bay Area Artists from the Svane Gift, on view at the de Young museum in 2023, displays works from the gift, "captures the local moment, as reported by KQED"[10] The de Young also organized the first-ever retrospective of Feminist Art pioneer Judy Chicago in 2020, forty years after her landmark installation The Dinner Party (1974–79) made its debut in San Francisco.

[11] Uncanny Valley: Being Human in the Age of AI organized at the de Young in 2021 was the "first major exhibition to unpack this question through a lens of contemporary art and propose new ways of thinking about intelligence, nature, and artifice.

[13] In 2021, the de Young organized artist Hung Liu's solo show, Golden Gate (金門), an exhibition that centered on the immigrant and migrant experience in California.

The de Young has exhibited fashion since the 1930s, with pieces by Dior, Balenciaga, Madame Grès, Yves Saint Laurent, Chanel, Ralph Rucci, and Kaisik Wong.

The exhibition explored Muslim female dress codes from multiple communities, cultures and religious interpretations, starting at the turn of the millennium.

The terrain and seismic activity in San Francisco posed a challenge for the designers Herzog & de Meuron and principal architects Fong & Chan.

To help withstand future earthquakes, "[the building] can move up to three feet (91 centimeters) due to a system of ball-bearing sliding plates and viscous fluid dampers that absorb kinetic energy and convert it to heat".

The entire exterior is clad in 163,118 sq ft (15,154.2 m2) of copper, which is expected to eventually oxidize and take on a greenish tone and a distinct texture to echo the nearby eucalyptus trees.

In order to further harmonize with the surroundings, shapes were cut into the top to reveal gardens and courtyards where 48 trees had been planted, the giant tree-ferns that form a backdrop for the museum entrance are particularly dramatic.