Agricultural intensification may accelerate the loss of wetlands, increasing the concentrations of nutrients and sediments in downstream water bodies. The objective of this study was to assess the effects of land use and land cover and river discharge on water quality in the Migina catchment, southern Rwanda. Rainfall, discharge and water quality (total nitrogen, total phosphorus, total suspended solids, dissolved oxygen, conductivity, pH, and temperature) were measured in different periods from May 2009 to June 2013. In 2011, measurements were done at the outlets of 3 sub-catchments (Munyazi, Mukura and Akagera). Between May 2012 and May 2013 the measurements were done in 16 reaches of Munyazi dominated by rice, vegetables, grass/forest or ponds/reservoirs. Water quality was also measured during two rainfall events. Results showed seasonal trends in water quality associated with high water flows and farming activities. Across all sites, the total suspended solids related positively to discharge, increasing 2–8 times during high flow periods. Conductivity, temperature, dissolved oxygen, and pH decreased with increasing discharge, while total nitrogen and total phosphorus did not show a clear pattern. The total suspended solids concentrations were consistently higher downstream of reaches dominated by rice and vegetable farming. For total nitrogen and total phosphorus results were mixed, but suggesting higher concentration of total nitrogen and total phosphorus during the dry and early rainy (and farming) season, and then wash out during the rainy season, with subsequent dilution at the end of the rains. Rice and vegetable farming generate the transport of sediment as opposed to ponds/reservoir and grass/forest.