He began working with his long-term collaborator Richard Hope Simpson in 1958, and the two expanded their efforts into the University of Minnesota Messenia Expedition between 1961 and 1975.

[2] From 1938 until 1939, McDonald was a student of the American School of Classical Studies in Athens and participated in excavations of the "Palace of Nestor" at Pylos and at Olynthos.

McDonald chose Nichoria because he believed that it was time for archaeologists to research more ordinary ancient remains rather than focus on recovering monumental sculptures, architecture, and other artistic artifacts that usually end up being displayed in museums.

McDonald's work at Nichoria first appeared in preliminary reports published in Hesperia, the journal of the American School of Classical Studies at Athens.

His account of Bronze Age archaeology in Greece entitled Progress into the Past: The Rediscovery of Mycenaean Civilization was written from both an historical and a biographical standpoint.

McDonald was always interested in exploring and developing new teaching methods and decided near the end of his career to stop lecturing and to focus instead on class discussions.

Shortly afterward, he contributed to establishing the Center for Ancient Studies, which was an interdisciplinary graduate program in archaeology that was an extension of the Minnesota Messenia Expedition.

[6] To honor his memory, many of his friends, colleagues, and students established the William A. McDonald Lectureship in Aegean Prehistory as part of the National Lecture Program of the Archaeological Institute of America.