Coal combustion residuals (CCR) from energy generation may pose a risk to human health and the environment if not managed properly. Because of new regulations for the management of CCR, generators must dispose of these materials in lined landfill units similar to municipal solid waste (MSW) landfills. Generators could opt to construct dedicated units for CCR (monofilling) or by placing them in MSW landfills (co-disposal). The distinct chemical environments of these two disposal scenarios may cause a noticeable difference in pollutant mobilization from CCR. Batch leaching tests were employed to simulate CCR monofilling and MSW co-disposal. Landfill leachate promoted higher release of As and V from fly ash compared to ash leached with synthetic rainwater. Changes in pH do not account for the added release and other characteristics intrinsic to MSW leachate play a dominant role. When fly ash disposal is modeled, As release is forecasted to be almost 690 tons under a co-disposal scenario, compared to 18 tons when ash is monofilled. These observations highlight the need for better long-term planning when deciding the disposal routes for municipal, commercial, and industrial byproducts.