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The Appalachian Mountains are arguably home to the highest degree of amphibian diversity in the world, particularly caudate (salamander) biodiversity. Despite the high degree of amphibian endemism in the Appalachians, several regions remain unsurveyed for amphibian species. In addition to this knowledge gap, we are in the midst of alarming amphibian biodiversity loss. Thus, it is of the utmost importance to bridge this knowledge gap by conducting surveys before some of these amphibian species are lost. We surveyed Wise County (previously unsurveyed county in the Appalachian Mountains with no records existing in the primary literature) over two years to assess amphibian species presence. We found 23 different species of amphibians (eight species of frogs and toads; 15 species of salamanders). In addition, we report five new amphibian species occurrences previously unreported in the primary literature within Wise County. However, not all amphibian species expected to occur in Wise County were observed. The primary suspected reason for their lack of occurrence involves habitat loss and/or modification, since the region is heavily exploited for coal and lumber. Overall, our study provides invaluable data in current times of amphibian biodiversity concern as they clarify and expand our knowledge of known amphibian species within the area. Using our work as a foundation, future surveying could assess whether amphibian biodiversity of Wise County are experiencing growth, stability, or decline.