This dataset includes the one-dimensional HEC-RAS water quality model simulation input and output files for two simulation discharges at the Lazy Day (LD) reach on the Big Piney River near St. Robert, Missouri. Simulations were run for environmental DNA (eDNA) sample collection dates on July 07, 2020 and July 23, 2021. For each eDNA collection date, the transport of freshwater mussel eDNA from Cumberlandia monodonta was simulated by specifying eDNA as an arbitrary constituent in the HEC-RAS water quality module and assigning a first order rate of decay. To account for the variation of the eDNA field samples at the upstream boundary condition, as well as the laboratory derived decay constants, we ran three model simulations for each eDNA collection date: a) the mean eDNA concentration at the upstream boundary with the mean decay constant (k), b) the mean eDNA concentration at the upstream boundary plus 1SE with the mean k minus 1SE, and c) the mean eDNA concentration at the upstream boundary minus 1SE with the mean k plus 1SE. Field collected eDNA concentrations were used as an upstream boundary condition.