Alice Walton approached art acquisition the way her father approached retail: methodically, with an eye for value. Art historian John Wilmerding, hired in 2005 for acquisition advice, noted that Walton would not spend at any cost. When artworks became available through private sales, she would often say, 'Wait. It will come to auction where we can get it at a better price' -- and she was usually right. By 2008, the museum's total art acquisitions exceeded $222 million. The collection spans American art from the Colonial era to the contemporary period: Charles Willson Peale's portrait of George Washington, Norman Rockwell, Georgia O'Keeffe, Andy Warhol's Coca-Cola [3] purchased for $57.3 million, Jasper Johns' Flag for $36 million, and a Mark Rothko acquired for nearly $45 million. In 2014, the museum even purchased and relocated a Frank Lloyd Wright house -- the Bachman-Wilson House -- dismantling it in New Jersey and reassembling it in Bentonville.

Israeli-Canadian architect Moshe Safdie designed the museum as a series of pavilions nestled into a natural ravine, connected by bridges that span two creek-fed ponds. The engineering firm Buro Happold helped realize Safdie's vision of a building that seemed to grow from the landscape rather than being imposed upon it. Architect Marlon Blackwell, an Arkansas-based designer, contributed the museum store. The complex includes galleries, meeting and classroom spaces, a library, and a sculpture garden where trails wind through native Ozark forest. The restaurant, named Eleven after the museum's opening date of 11/11/11, overlooks the ponds. The museum employs approximately 300 people and is within walking distance of downtown Bentonville.

In May 2011, the Walton Family Foundation announced three endowments totaling $800 million: $350 million for operating expenses, $325 million for acquisitions, and $125 million for capital improvements. By July 2023, the museum's listed assets exceeded $1.7 billion. Crystal Bridges was the first major art museum with an endowment over $200 million to open in the United States since 1974. A 2023 grant of $7 million from the Walmart Foundation ensures free admission through 2028, continuing a tradition of accessibility established at opening. The museum has collaborated with the Louvre in Paris, the High Museum of Art in Atlanta, and the Terra Foundation for American Art on a rotating exhibition series called American Encounters. In 2020, Crystal Bridges opened a satellite facility called The Momentary, focused on contemporary visual and performing arts.

The museum's permanent collection tells the American story through paint, stone, and steel. Gilbert Stuart's 1797 portrait of Washington hangs in galleries near works by Thomas Cole, Mary Cassatt, and Albert Bierstadt. Sculpture lines outdoor trails: Roxy Paine's tree-like stainless steel forms, Mark di Suvero's monumental abstractions, and James Turrell's immersive light installations. The collection features works by Vanessa German and Kerry James Marshall alongside Jackson Pollock and Andrew Wyeth. Wilmerding assessed that the museum ranks among the top half-dozen American art museums in quality, range, and depth. For a region better known for poultry farms and discount retail, Crystal Bridges has reshaped the cultural geography of the American South -- proof that world-class art need not cluster only on the coasts.