The Araguari River basin has a huge water resource potential. However, population and industrial growth have generated numerous private and collective conflicts of interest in the multiple uses of water, resulting in the need for integrated management of water quantity and quality at the basin scale. This study used the AQUATOOL Decision Support System. The water balance performed by the SIMGES module for the period of October 2006 to September 2011 provided a good representation of the reality of this basin. The parameters studied were dissolved oxygen, biochemical oxygen demand, organic nitrogen, ammonia, nitrate and total phosphorus. The coefficients of biochemical reactions, sedimentation rates and sediment dissolved oxygen release for this period were calibrated and validated in the quality modeling using the GESCAL module. A sensitivity analysis indicated that the coefficients of carbonaceous matter decomposition, nitrification, water temperature, and sediment oxygen demand interfered more significantly in the variables of state. To prevent eutrophication in the Nova Ponte reservoir and in the other cascade reservoirs, the local River Basin Committee should adopt restrictive actions against the use of agricultural fertilizers. On the other hand, in the sub basin of the Uberabinha River, new alternatives for public water supply to the city of Uberlândia and improvements in the treatment efficiency of the main wastewater treatment plant (WWTP) should be proposed, since the biochemical oxygen demand, ammonia and total phosphorus failed to meet the requirements of COPAM (2008) in the driest months.