Pollution is a major, overlooked, global health threat that was responsible in 2015 for an estimated 9 million deaths and great economic losses. To end neglect of pollution and advance prevention of pollution-related disease, we formed the Lancet Commission on Pollution and Health. Despite recent gains in understanding of pollution and its health effects, this Commission noted that large gaps in knowledge remain. To close these gaps and guide prevention, the Commission made research recommendations and proposed creation of a Global Observatory on Pollution and Health. We posit that successful pollution research will be translational and based on transdisciplinary collaborations among exposure science, epidemiology, data science, engineering, health policy, and economics. We envision that the Global Observatory on Pollution and Health will be a multinational consortium based at Boston College and the Harvard T.H. Chan School of Public Health that will aggregate, geocode, and archive data on pollution and pollution-related disease; analyze these data to discern trends, geographic patterns, and opportunities for intervention; and make its findings available to policymakers, the media, and the global public to catalyze research, inform policy, and assist cities and countries to target pollution, track progress, and save lives. https://doi.org/10.1289/EHP3141.