||Agricultural development is critical for economic growth and food security. However, sediment and nutrient runoff generated by farming may cause pollution and water quality deterioration. This study assessed the water quality effects of conversion of valley bottom wetlands to agriculture in southern Rwanda. Three land use/cover (LULC) types (fishponds, rice, wetland plots) were studied in a replicated mesocosm setup. LULC characteristics (hydrology, biomass growth) and practices (land preparation, feed/fertilizer application) and associated changes in total nitrogen and phosphorus (TN, TP), suspended solids (TSS), and other water quality characteristics were measured from 2011 to 2013. Fish farming used about half the amount of water compared to rice farming (101 mm m−2 d−1 compared with 191 mm m−2 d−1). Higher TSS, TP and TN in inflows and outflows were associated mainly with human activities (cleaning of canals, ploughing, weeding, fertilizer application, fishpond drainage and dredging). As a result, fishponds and rice plots had consistently higher TSS concentrations in outflows (5-9506 and 7-2088 mg/L, respectively) than in inflows (7-120 and 9-483 mg/L, respectively). Peaks in TN and TP were associated with periods of farming activity. In wetland plots, TSS and TN significantly decreased from inlet to outlet, owing to the absence of disturbances and higher settling/adsorption, nutrient uptake and denitrification. Environmental restoration and sustainable agricultural production would be promoted by conservation farming and efficient water and fertilizer use. It is worth exploring the integration of fishponds for temporary storage of water, sediments and nutrients, and of natural wetlands as buffer zones for sediments and nutrients from farming during the critical periods of agricultural activity.