Arboviruses are caused by a group of viruses spread to people (host) by the bite of infected insects (vector). It is within these hosts that arboviruses replicate and undergo genomic evolution. However, how arboviruses evolve, are transmitted, or cause disease in nature remain unclear. Therefore, this study established a Zika virus (ZIKV) vector-borne transmission system in immunocompromised mice to study the characteristics of ZIKV infection. This study also identified the emergence of ZIKV mutants in mice previously seen in natural infections as well as mutations unique to the mouse infections. The dataset contains sequencing data. The publication also has supplementary data, which includes several tables. The tables contain data about ZIKV primers, ZIKV MR766 consensus changes identified, minority variants found in viral stocks, MR766 minority variants present in currently circulating ZIKV strains, and natural minority variants.