Compost amendments and tillage practices can modify soil structure and create heterogeneities at the local scale. Tillage affects soil physical properties and consequently water and solute transport in soil, while compost addition to soil influences pesticide sorption and degradation processes. Based on the long-term field experiment QualiAgro (a INRA–Veolia partnership), a modeling study was carried out using HYDRUS-2D to evaluate how two different compost types combined with the presence of heterogeneities due to tillage affect water and isoproturon dynamics in soil compared to a control plot. A municipal solid waste compost (MSW) and a co-compost of sewage sludge and green wastes (SGW) have been applied to experimental plots. In each plot, wick lysimeters, TDR probes, and tensiometers were installed to monitor water and solute dynamics. In the plowed layer, four zones differing in their structure were identified: compacted clods, non-compacted soil, interfurrows, and the plow pan. From 2004 to 2010, the unamended control (CONT) plot had the largest cumulative water outflow (1388 mm) compared to the MSW plot (962 mm) and SGW plot (979 mm). After calibration, the model was able to describe cumulative water outflow for the whole 2004–2010 period with a model efficiency value of 0.99 for all three plots. The CONT plot had the largest isoproturon cumulated leaching (21.31 μg) while similar cumulated isoproturon leaching was measured in the SGW (0.663 μg) and MSW (0.245 μg) plots. The model was able to simulate isoproturon leaching patterns except for the large preferential flow events that were observed in the MSW and CONT plots. The timing of these preferential flow events could be reproduced by the model but not their magnitude. Modeling results indicate that spatial and temporal variations in pesticide degradation rate due to tillage and compost application play a major role in the dynamics of isoproturon leaching. Both types of compost were found to reduce isoproturon leaching on the 6 year duration of the experiment.