Showcasing sacred and secular Indigenous art and artifacts in the Hall of North America, Pope Pius XI’s 1925 Missionary Exhibition attracted over one million visitors from around the world. This project analyzes the visual and material culture displayed at the 1925 Vatican Missionary Exhibition, comprising cultural belongings made by Indigenous American artists and settler artists’ representations of Indigenous Americans collected by missionaries. The exhibition was the first of its kind at the Vatican: never had an exposition exclusively showcased missionary activities and Indigenous arts for a global audience. Presenting historiography of the visual culture of First Peoples as expressed at the 1925 Exhibition—surveying statuary, children’s games, and archival materials as well as cultural belongings—this research explores the mobility and sovereignty of Indigenous artists, travelers and activists in the Eternal City.