The water quantity and quality in two of the four main drainage canals located in the plain of Chryssoupolis in Kavala, North Greece, are studied. The area is intensively used for agriculture. Irrigation water is supplied by Nestos River, using a network of irrigation canals. Drainage water and irrigation return flows are collected in the four main drainage canals, which outflow into the Thracian Sea, North Aegean. A monitoring program in the four canals was designed to monitor flow and main constituents of drainage water. Main pollutants included nitrate, phosphorus and suspended solids. Based on the collected data, the trophic state of the canals and its seasonal variation were assessed, and the limiting nutrient was identified. QUAL2Kw was also used to model flow and water quality in two of the four canals. The calibration and verification of QUAL2Kw was undertaken using the collected field data, in an effort to identify the pollution sources and propose future management actions for the improvement of drainage canal water quality. The results showed that QUAL2Kw is a useful tool to simulate water quality in rivers and canals, and to quantify the impacts of non-point source pollution from agricultural areas.