Whether on an urban or planetary scale, covering time scales of a few minutes or a few decades, the societal need for more accurate weather, climate, water, and environmental information has led to a more seamless thinking across disciplines and communities. This challenge, at the intersection of scientific research and society’s need, is among the most important scientific and technological challenges of our time. The “Science Summit on Seamless Research for Weather, Climate, Water, and Environment” organized by the World Meteorological Organization (WMO) in 2017, has brought together researchers from a variety of institutions for a cross-disciplinary exchange of knowledge and ideas relating to seamless Earth system science. The outcomes of the Science Summit, and the interactions it sparked, highlight the benefit of a seamless Earth system science approach. Such an approach has the potential to break down artificial barriers that may exist due to different observing systems, models, time and space scales, and compartments of the Earth system. In this context, the main future challenges for research infrastructures have been identified. A value cycle approach has been proposed to guide innovation in seamless Earth system prediction. The engagement of researchers, users, and stakeholders will be crucial for the successful development of a seamless Earth system science that meets the needs of society.