To promote urban sustainability and resilience, there is an increasing demand for actionable science that links science and decision making based on social–ecological knowledge. Approaches, frameworks, and practices for such actionable science are needed and have only begun to emerge. We propose that approaches based on the co-design and co-production of knowledge can play an essential role to meet this demand. Although the antecedents for approaches to the co-design and co-production of knowledge are decades old, the integration of science and practice to advance urban sustainability and resilience that we present is different in several ways. These differences include the disciplines needed, diversity and number of actors involved, and the technological infrastructures that facilitate local-to-global connections. In this article, we discuss how the new requirements and possibilities for co-design, co-production, and practical use of social–ecological research can be used as an ecology for the city to promote urban sustainability and resilience. While new technologies are part of the solution, traditional approaches also remain important. Using our urban experiences with long-term, place-based research from several U.S. Long-Term Ecological Research sites and U.S. Department of Agriculture, Forest Service Urban Field Stations, we describe a dynamic framework for linking research with decisions. We posit that this framework, coupled with a user-defined, theory-based approach to science, is instrumental to advance both practice and science. Ultimately, cities are ideal places for integrating basic science and decision making, facilitating flows of information through networks, and developing sustainable and resilient solutions and futures.