Frank Gehry was commissioned to design this museum shortly after his Walt Disney Auditorium project was cancelled in its initial stages. This experience influenced the design of the Guggenheim Museum, as it shared a similar conceptual approach with his original auditorium project. The organic, flowing forms that characterize the museum originated in Gehry's earlier works, beginning with the Vitra Museum and continuing in other projects. During the conception of the museum, Gehry created numerous hand-drawn models to explore possible forms for the building.

All of these models have been on display since July 1995 in an exhibition called "Peggy Guggenheim," which is housed in a historic building in Venice. Although Gehry did not use a computer in his design process, his team did. They digitized Gehry's models by adapting a computer program called Catia, developed by Dassault Systèmes, to apply these forms to architectural design. The adaptation of this program to architecture was costly, and the Guggenheim Foundation covered these expenses.