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Land cover change is prevalent in the eastern Kentucky Appalachian region, mainly due to increased surface mining activities. This study explored the potential change in land cover and its relationship with stream discharge and sediment yield in a watershed of the Cumberland River near Harlan, Kentucky, between 2001 and 2016, using the Soil and Water Assessment Tool (SWAT). Two land cover scenarios for the years 2001 and 2016 were used separately to simulate the surface runoff and sediment yield at the outlet of the Cumberland River near Harlan. Land cover datasets from the National Land Cover Database (NLCD) were used to reclassify the land cover type into the following classes: water, developed, forest, barren, shrubland, and pasture/grassland. Evaluation of the relationship between the land cover change on discharge and sediment was performed by comparing the average annual basin values of streamflow and sediment from each of the land cover scenarios. The SWAT model output was evaluated based on several statistical parameters, including the Nash–Sutcliffe efficiency coefficient (NSE), RMSE-observations standard deviation ratio (RSR), percent bias (PBIAS), and the coefficient of determination (R²). Moreover, P-factor and R-factor indices were used to measure prediction uncertainty. The model showed an acceptable range of agreement for both calibration and validation between observed and simulated values. The temporal land cover change showed a decrease in forest area by 2.42% and an increase in developed, barren, shrubland, and grassland by 0.11%, 0.34%, 0.53%, and 1.44%, respectively. The discharge increased from 92.34 mm/year to 104.7 mm/year, and sediment increased from 0.83 t/ha to 1.63 t/ha from 2001 to 2016, respectively. Based on results from the model, this study concluded that the conversion of forest land into other land types could contribute to increased surface runoff and sediment transport detached from the soil along with runoff water. The research provides a robust approach to evaluating the effect of temporal land cover change on Appalachian streams and rivers. Such information can be useful for designing land management practices to conserve water and control soil erosion in the Appalachian region of eastern Kentucky.