Rice (Oryza sativa L.) is cultivated in large river basins in Europe, where high loads of applied herbicides have resulted in the contamination of related surface water (SW) and groundwater (GW) systems. Therefore, risk assessment of pesticides used on rice should be performed at the basin scale. This study reports the development and validation of a basin-scale scenario, representative of rice cultivation in the main rice cultivation area in Greece, the Axios river basin. Soils of the rice-cultivated region of the basin are characterized as heavy clay, clay loams with poor infiltration. A 2000-ha rice-cultivated basin was simulated consisting of rice management blocks (200 ha) associated with drainage canals and a cross-linked river. This system was conceptualized using a combination of rice water quality (RICEWQ 1.6.2v) and river water quality (RIVWQ 2.02) models. Application of RICEWQ 1.6.2v for a 20-yr simulation period showed that the 90th percentile of the annual GW predicted environmental concentrations (PECs) for the herbicides propanil (3′,4′-dichloropropionanilide) and molinate (S-ethyl perhydroazepine-1-carbothioate) were 3.2 fg L−1 and 1.9 pg L−1, respectively, suggesting low risk to GW. Pesticide mass and water releases from simulated paddies were utilized as inputs for canals and river, and the fate of propanil and molinate was simulated with the RIVWQ model. Comparison of the 90th percentile of maximum daily river PECs with the maximum measured concentrations of propanil and molinate in the Axios river in 1994 revealed acceptable agreement in both the magnitude of values and their temporal distribution. In general, the 90th percentiles of the maximum daily PECs of propanil in both canals (1.96 μg L−1) and rivers (1.15 μg L−1) were markedly lower than the corresponding PECs of molinate (6.07 and 0.394 μg L−1, respectively). Increases in the period of paddy closure after application of molinate resulted in reduced SW PECs, suggesting that the selection of water management practices should be done according to pesticide persistence and local agronomic conditions.