The current challenge in sustainable agriculture is to redesign cropping systems aiming at reducing the use and impacts of pesticides, and therefore to protect the environment, in particular groundwater, and human health. As a large range of systems could be explored and a wide number of pesticides used, field experiments cannot be carried out to study the sustainability of each of them. Thus, the objective of this work was to evaluate and to compare the ability of three pesticide fate recognized models (MACRO, PEARL, PRZM) to simulate the water and pesticide flows observed in six contrasted innovative cropping systems based on maize monoculture, oilseed rape-wheat-barley rotation, and sunflower-wheat rotation, experimented for three years in three different soil and climatic conditions. The innovative systems were designed with different crop rotations, cover crops, and intercrops. A method was firstly developed to parameterize intercrops which were not explicitly represented in the models: the use of average crop factors, maximum LAI, and maximum crop height and rooting depth of the crops constituting the intercrop allowed acceptable simulations of cumulated water flows, but not their dynamic. Twelve different pesticides over 70 applied were detected in the lysimeters (e.g., bentazone, glyphosate, S-metolachlor), their concentrations exceeded 0.1 µg L-1 in several situations. The performance of the models to reproduce pesticide concentrations was poor though “worst-case” values of pesticide sorption and degradation parameters (i.e., minimum Kf values, maximum nf and DT50 values) were mostly used, illustrating the great challenge and the progress needed to simulate accurately pesticides transfer into the soil. Overall, MACRO was found to be the most efficient models followed by PEARL and PRZM. The method developed in this work could be used for risk assessment of groundwater contamination by pesticides in innovative cropping systems, considering the risk is likely to be underestimated in some situations.