Large-scale changes in land use are occurring in many tropical regions, with significant impacts on nitrogen and phosphorus biogeochemistry. In this study we examine the relationships between land use, anthropogenic nutrient inputs, and riverine nutrient exports in a major agricultural watershed of the Pacific coast of South America, the Guayas River basin of Ecuador. We present comprehensive nutrient budgets for nitrogen (N) and phosphorous (P) for the Guayas River basin and 10 sub-watersheds. We quantify the four major anthropogenic nutrient fluxes into and out of the region: N and P fertilizer application, N fixation by leguminous crops, net import/export of N and P in agricultural products (food and feed), and atmospheric deposition. We also estimate inputs of N from biological N fixation in forests and of P from weathering sources in soils and bedrock. The sum of these sources represents net inputs of N and P to each watershed region. Overall, synthetic fertilizers are the largest input to the Guayas Basin for N (53%) and P (57%), and the largest outputs are N and P in crops. Losses of N and P in river export account for 14-38% of total N and P inputs, and there is significant accumulation of N and P, or unmeasured forms of N and P export, in most of the sub-basins. Nutrient balances are indicative of the sustainability of land use practices in a region, where a negative balance of N or P indicates nutrient depletion and subsequent loss of soil fertility, yield, and economic viability. Although the nutrient balance of the entire Guayas Basin is positive, there are negative or near zero balances in two sub-watersheds with extensive banana, coffee and permanent crops. In these basins, degradation of soil quality may be occurring due to these net nutrient losses. Our data show that nutrients are leaving the basin primarily as export crops, with riverine losses of nutrients smaller than crop exports. Nonetheless, there is a direct relationship between nutrient inputs and river outputs, suggesting that agricultural management practices in the basin may have direct impacts on N and P delivery to the highly productive Guayas estuary.