The low-gradient, forested wetland landscape of the southeastern United States’ Coastal Plain represents an important eco-hydrologic system, yet there is a very little information available on the region’s ecological, hydrological and biogeochemical processes. Long-term hydrologic monitoring can provide the information needed to understand basic hydrologic processes and their interactions with climatic variation, ecosystem processes, land use change, and other natural and anthropogenic disturbances. Monitoring also provides researchers with baseline data for evaluating responses, generating new scientific hypotheses, and testing eco-hydrologic models. This information is crucial for the sustainable management of present and future water resources in the southeastern Coastal Plain region, with its growing population, rapidly expanding development, and intensive timber and agricultural industries. This paper presents a multi-collaborative approach for building a monitoring and modeling framework for conducting long-term eco-hydrological studies on a 5,000 ha watershed in the South Carolina Coastal Plain.