The Museum houses one of the largest collections of Egyptian and Nubian material in the United States, with more than 42,000 items. Assembled through nearly a century of archaeological research, this collection is unusual in that a majority of the objects were obtained through archaeological investigations in Egypt. Because the museum has worked at a wide range of sites (provincial and royal cemeteries, palaces, temples, towns, sanctuaries and settlements), the collection spans ancient Egypt's entire history, from the Predynastic Period (circa 4000 BCE through the Greco-Roman Period and into the Coptic Period (ending in the 7th century CE). It also includes a large number of material categories, such as architecture, statuary, minor arts, domestic artifacts, textiles, papyri, pottery, tools, jewelry, weapons, funerary objects and human remains.

A major part of the collection, however, results from excavations sponsored by the Penn Museum. The Museum sponsored excavations in settlements and cemeteries in Nubia; at Egypt's ancient capital city of Memphis (Mit-rahina); in the cemeteries at Dendera, Giza, Dra' Abu el-Naga (near Thebes), and Meidum; and at the major cult center of Abydos, among others. Before originating its own excavations, the Penn Museum contributed funding to support the work of the Egypt Exploration Fund (later Egypt Exploration Society), a British organization responsible for archaeological excavations throughout Egypt. In particular, it funded the work of Sir William M. Flinders Petrie, one of the foremost archaeologists working in Egypt at the time. As a result, the Museum obtained a significant portion of the material awarded to this project by the Egyptian government. Among the most important artifacts are the Predynastic and Early Dynastic remains, which document the earliest periods of Egyptian history and the formation of the unified state.