It was founded by Isabella Stewart Gardner, whose will called for her art collection to be permanently exhibited "for the education and enjoyment of the public forever."

An auxiliary wing designed by Italian architect Renzo Piano, adjacent to the original structure near the Back Bay Fens, was completed in 2012.

The museum opened on January 1, 1903, with a grand celebration featuring a performance by members of the Boston Symphony Orchestra and a menu that included champagne and doughnuts.

During Gardner's lifetime, she welcomed artists, performers, and scholars to Fenway Court to draw inspiration from the rich collection and dazzling Venetian setting, including John Singer Sargent, Charles Martin Loeffler, and Ruth St. Denis, among others.

When Gardner died in 1924, her will created an endowment of $1 million and outlined stipulations for the support of the museum, including the charge that her collection be permanently exhibited "for the education and enjoyment of the public forever" according to her aesthetic vision and intent.

Early in the morning of March 18, 1990, two thieves disguised as police officers robbed the museum of thirteen works worth some $500 million – the greatest known property theft in history.

[citation needed] The statute of limitations on the theft has expired but criminal charges could be laid if an individual is found to be in possession of stolen property.

[10] In 2002, after a two-year master planning process, the museum's board of trustees determined that a new wing was necessary to preserve the historic building and to provide improved spaces for programs that continue Isabella Gardner's legacy.

[13] The new expansion includes spaces for visitor services, concerts, special exhibitions, and education and landscape programs, furthering Isabella Gardner's legacy in art, music, and horticulture while reducing 21st-century strain on the collection and galleries.

[13] Built to evoke a 15th-century Venetian palace, the museum building provides an atmospheric setting for Gardner's inventive creation.

Gardner hired Willard T. Sears to design the building near the marshy Back Bay Fens to house her growing art collection.

[16] It was built from the ground up in Boston out of new materials, though it incorporates numerous architectural elements removed from European Gothic and Renaissance structures, worked into the design of the turn-of-the-century building.

Well-known artworks in the museum's collection include Titian's The Rape of Europa, John Singer Sargent's El Jaleo and Portrait of Isabella Stewart Gardner, Fra Angelico's Death and Assumption of the Virgin, Rembrandt's Self-Portrait, Aged 23, Cellini's Bindo Altoviti, Piero della Francesca's Hercules, and Botticelli's The Story of Lucretia.

Eliot, Sarah Bernhardt, and Oliver Wendell Holmes, in addition to travel albums, dealer receipts, and guest books.

The museum regularly produces scholarly exhibitions, lectures, family programs, and symposia that provide insights into the historic collection.

The Gardner's concert series welcomes musicians and emerging artists to perform classical masterpieces, new music, and jazz on Sunday afternoons and select Thursday evenings.