Groundwater quality can be impacted through the backfilling of coal pits with waste rock containing new mineral surfaces and transportable particles. Reaction fronts may propagate with the saturation of these backfill aquifers as the previously bound minerals and newly created nanomaterials provide additional release of potential contaminants. This study was implemented to identify newly available arsenic and selenium sources and effectively model their release with the weathering of waste rock from the Cordero Rojo Mine in the Powder River Basin, Wyoming. Basic forward models were constructed to replicate the typical modeling scenario for the identified mineral sources of arsenic and selenium in the Powder River Basin overburden—pyrite and gypsum, respectively. The basic forward models were unable to capture the arsenic and selenium trends recorded for leachate from a kinetic column loaded with waste rock from the Cordero Rojo Mine. Enhanced models were constructed to capture nanomaterial contributions to supplement the initially identified processes of the oxidation of arsenic-bearing pyrite and dissolution of selenium-bearing gypsum. Incorporation of the nanomaterial contributions produced modeled arsenic and selenium trends similar to the observed trends in the column leachate. The identification and modeling of newly available contaminant sources in backfill waste rock is necessary to predict the exceedance of water quality criteria for overburden formations that have not previously shown the potential for water quality contamination.