Founded by physicist and educator Frank Oppenheimer in 1969, the museum was originally located in the Palace of Fine Arts and was relocated in 2013 to Piers 15 and 17 on San Francisco's waterfront.

Back in the United States, Oppenheimer was invited to do the initial planning for a new branch of the Smithsonian, but he eventually turned it down to work instead on what he called his "San Francisco project".

Oppenheimer sought funding and support for the endeavor using a grassroots approach, bringing a written proposal and some handmade exhibits with him as he visited scientists, businesses, city and school officials, relatives, and friends.

Many prominent scientists and cultural figures endorsed the project, and the offers of support, in conjunction with a $50,000 grant from the San Francisco Foundation, made the museum realizable.

Chris Flink served as director from June 2016[8] through February 2022, when he was replaced by the former Chancellor of the University of North Carolina School of the Arts (UNCSA) and PBS executive, Lindsay Bierman.

This infill was removed as part of the construction phase, restoring the space between the piers to public plazas, a pedestrian bridge, and open water.

This second joint ensures that the entire pier will move independently from the land mass in the event of an earthquake, significantly reducing the potential torsional stress.

[25][26] In addition to solar power, the museum makes use of an HVAC system that takes advantage of the relatively constant, moderate temperature of the bay water under the piers, which is 50 to 65 °F (10 to 18 °C), to heat and cool the building.

By integrating radiant heating and cooling and displacement ventilation, the Exploratorium has greatly reduced the portion of its HVAC system that relies on forced air.

Two large cisterns under the structural beams connecting the southeast pilings capture up to 338,000 US gallons (1,280 m3) of rainwater and fog runoff for reuse in the facility.

In compliance with historic preservation requirements, the building’s façade was left mostly unchanged, allowing for much of the interior space to benefit from the existing architecture’s ample daylight.

[34] According to the New York Times, "After a two-year post-opening shakedown period of monitoring and adjusting the systems, the Exploratorium hopes to become the largest net-zero-energy-use museum in the United States and possibly the world.

Exhibits cover a range of subject areas, including human perception (such as vision, hearing, learning and cognition), the life sciences, physical phenomena (such as light, motion, electricity, waves and resonance, and magnetism), local environment (water, wind, fog, rain, sun, and other elements, as well as cityscape, landscape, and the flora and fauna of the Bay) and human behavior (such as cooperation, competition, and sharing).

Its signage and exhibits encourage visitors to play with perception; investigate memory, emotion, and judgment; and experiment with how people cooperate, compete, and share.

It holds exhibits such as Poker Face (partners try to assess when someone is bluffing), Trust Fountain (an experimental exhibit from the museum’s National Science Foundation-funded Science of Sharing project, this two-person drinking fountain is based on the Prisoner’s dilemma, a classic scenario centering on negotiation and trust),[38] and the Tactile Dome, a pitch-black single-path maze environment visitors explore by touch, which was originally designed by Carl Day, August Coppola, producer.

[39] Gallery 1 also included the temporary exhibition The Changing Face of What is Normal: Mental Health, which showcased the personal artifacts of patients from the now-decommissioned Willard Psychiatric Center,[40] which was on view through April 2014.

Artworks on display include the Tinkerer’s Clock (a 22-foot-high clock constructed by artist Tim Hunkin, with figurines in his noted cartoon style that can be manipulated by visitors and unfold into a clockface on the hour); and Rolling Through The Bay (a sculpture made by artist Scott Weaver over the course of 37 years, utilizing over 100,000 toothpicks and depicting many of the Bay Area’s iconic landmarks, through which a ping-pong ball can roll on one of several different "tours").

[53] The lower level of the Bay Observatory Building houses the Seaglass Restaurant, which, like the Seismic Joint Cafe, is open to unticketed members of the public.

Parodying the cult Japanese TV program, Iron Chef, this competition showcases science teachers as they devise classroom activities using a particular ingredient — an everyday item such as a plastic bag, milk carton, or nail.

[59] The Institute for Inquiry partnered with the Sonoma Valley Unified School District on a program combining science education with English Language Development (ELD).

[60] The Center for Informal Learning and Schools (CILS) is a collaboration between the Exploratorium, the University of California Santa Cruz, and King's College London.

Lifelong Learning programs further the Exploratorium’s stated dedication to informal learning and the museum as teaching tool, and include day camps, workshops for families, the Homeschool Science series (in-house classes geared specifically towards homeschooled students), the Girl’s Science Institute (multi-day workshops geared towards girls 9–11), and excursions for adults.

The Exploratorium has also published a number of books, and many of the 50,000 pages on its website are hands-on activity ideas or science experiments in the museums’ signature open-ended style.

[66] The Exploratorium Explainer program, which has been operating since the museum opened, hires and trains high school students and young educators each year.

As early as 1966, Frank Oppenheimer presented a paper discussing the connections between art and science, and the role of a museum in appealing to both casual visitors and serious students of all ages.

[3]: 142 The formal artist in residence program was started in 1974,[73] but artworks such as Bob Miller’s Sun Painting were commissioned shortly after the museum was opened in 1969.

Artists are given a stipend, housing, travel expenses, and technical support, and they have at their disposal the Exploratorium's full array of metal and woodworking shops and materials.

The new Embarcadero campus opened with more than 40 pieces by prominent artists, including Douglas Hollis, Golan Levin, Lucky Dragons, Amy Balkin, and Fujiko Nakaya.

Participating artists and performers included Laurie Anderson, John Cage, Philip Glass, Steve Reich, Brian Eno, Ali Akbar Khan, Trimpin, and The Mermen.

Notable Osher Fellows have included Walter Murch, James P. Crutchfield, Christian de Duve, Arthur Ganson, Tim Hunkin, Lewis Hyde, Evelyn Fox Keller, Guillermo Gómez-Peña, Rosamond Wolff Purcell, Oliver Sacks, Mierle Laderman Ukeles, and Juan Felipe Herrera.