Abstract Sanitation coverage in the Republic of Panama is 5 to 10 percent below the Millennium Development Goals targets set for the country. Population growth, urbanization, unplanned development and waste mismanagement have resulted in improvised trash sites and waste discharges into river systems that are important components of the biologically diverse natural environment of Panama. The study sought to investigate and estimate the burden of waste from domestic and agricultural sources in three regions of the Chilibre corrigimiento (district). It was hypothesized that the water quality and land cover data would reflect that the most populated region in the study sample (Region 2) would have more water quality violations than the adjacent background and attenuation regions (Region 1 and Region 3) in the study sample. The results supported that Region 2 had the most water quality violations -- particularly at the CHIL 3 monitoring station. Based on the results the most appropriate best management practices (BMPs) were recommended for the household, community, watershed, and regional level waste management in the study region. Future research will look determine the effectiveness of microfinance programs in bolstering sanitation-based entrepreneurship in Chilibre and across Panama.