Heterogeneity in physical and chemical properties is a common characteristic in a subsurface environment. This study investigated the effect of physico-chemical heterogeneity on arsenic (As) sorption and reactive transport under water extraction in a layered system with preferential flow paths. A flume experiment was performed to derive the spatio-temporal data of As reactive transport. The results indicated that the heterogeneous system significantly accelerated downward (vertical direction) As migration as a coupled effect of physical and chemical heterogeneity that led to fast As transport with low As sorption along the preferential flow paths. The results also indicated that such a heterogeneity effect was driven by water extraction that enhanced the downward groundwater flow along the preferential flow paths. Numerical simulations were performed by matching the experimental results to provide insights into the dominant processes controlling the As migration in the heterogeneous systems. The simulation results highlighted the importance of the kinetic oxidation of mineral-bonded Fe(II) to Fe(III) in the clay matrix that dynamically increased As sorption affinity and retarded As reactive transport. A coupled model of reactive transport along the preferential flow paths, sorption-retarded diffusion from the preferential flow paths into the clay matrixes, and reactions that change sorption affinity in the matrix was required to describe the As reactive transport systems with physico-chemical heterogeneities. The results have strong implications for understanding and modeling As downward migration from shallow to deep aquifers under groundwater pumping conditions in field systems with inherent heterogeneity.