In the Southeast Asia region, arsenic contamination of groundwater has been reported in several countries and a large number of arsenic treatment units were installed in many regions. Microbial activity can greatly affect the mobilization of arsenic under anaerobic conditions when coupled with the oxidation of organic matter. In this study, a mathematical model was developed to predict the bioleaching of arsenic in response to organic matter contamination in the treatment unit. Calibration of the model was performed using the data of batch experiments, and finally the results obtained from the laboratory experiments were used to verify the developed model. The microbial decomposition of organic matter led to an anaerobic condition within the accumulated sludge in the sand filter and hence caused the bioleaching of arsenic. Under the inoperative condition of the treatment unit for 5, 10, and 15 days along with organic matter contamination of 15 mg/L as biochemical oxygen demand, the concentrations of bioleached arsenic were found to be 59, 184, and 275 μg/L, respectively. This study revealed the bioleaching potential of arsenic due to organic matter inclusion in the treatment process, which might contribute in designing safe options for drinking water.