Mooney's major interest is global Earth crustal structure and tectonics, with a focus on the continental lithosphere. Mooney has led fieldwork throughout North and South America. According to Mooney his international research collaborations have "provided both a rich basis for my science, and a broad cultural understanding.’ He has co-authored more than 170 scientific papers.

With Claus Prodehl of Universität Karlsuhe, Germany, Mooney wrote Exploring the Earth's Crust - History and Results of Controlled-Source Seismology).

Since 2011, he has been collaborating with the Saudi Geological Survey in a study of the crustal and upper mantle structure beneath western Saudi Arabia using data from the SGS broadband seismic network.