This article summarizes the primary outcomes of an interdisciplinary workshop in 2010, sponsored by the U.S. National Science Foundation, focused on developing key questions and integrative themes for advancing the science of human–landscape systems. The workshop was a response to a grand challenge identified recently by the U.S. National Research Council (2010a)—“How will Earth’s surface evolve in the “Anthropocene?”—suggesting that new theories and methodological approaches are needed to tackle increasingly complex human–landscape interactions in the new era. A new science of human–landscape systems recognizes the interdependence of hydro-geomorphological, ecological, and human processes and functions. Advances within a range of disciplines spanning the physical, biological, and social sciences are therefore needed to contribute toward interdisciplinary research that lies at the heart of the science. Four integrative research themes were identified—thresholds/tipping points, time scales and time lags, spatial scales and boundaries, and feedback loops—serving as potential focal points around which theory can be built for human–landscape systems. Implementing the integrative themes requires that the research communities: (1) establish common metrics to describe and quantify human, biological, and geomorphological systems; (2) develop new ways to integrate diverse data and methods; and (3) focus on synthesis, generalization, and meta-analyses, as individual case studies continue to accumulate. Challenges to meeting these needs center on effective communication and collaboration across diverse disciplines spanning the natural and social scientific divide. Creating venues and mechanisms for sustained focused interdisciplinary collaborations, such as synthesis centers, becomes extraordinarily important for advancing the science.