One of the major waterways in Serbia is the hydro-system Danube-Tisa-Danube (HS DTD) in the Province of Vojvodina. Since its water quality has been significantly deteriorated, especially on some reaches, the aim of the paper is to test a combined approach based upon leading European and United States concepts for assessment and better management within the hydrosystem. Transport and transformation of nutrients, including nitrogen compounds, NH4-N and NH3-N, and total phosphorous, have been modeled for one of the most polluted reaches of the canal Becej-Bogojevo. Modeling of the watercourse applied QUAL2K water quality modeling tool. Calibration of the model and subsequent validation required series of field measurements, including hydrometric measurements, quality parameters of the water samples and meteorological data. The developed model of the system was applied for analyzing different possible scenarios where water quality and hydrometric historical data were used as inputs. Obtained results gave an insight in the behavior of these pollutants in the investigated aquatic surrounding. Application of the methodology could form a basis for integral management of the pollution in the whole canal network of the HS DTD. By producing a pattern of source allocation, i.e. sharing of the pollution loading among the sources, it would contribute in the process of attaining the compliance with standards.