(1) Introduction. A recent viral outbreak of novel coronavirus (CoVID-19) was declared as a pandemic by the World Health Organization (WHO) due to its global public health concern. There has been an aggressive growth in the number of emerging cases suggesting rapid spread of the virus. Since the first reported case of CoVID-19, there has been vast progress in understanding the dynamics of CoVID-19. However, there is an increasing evidence of epidemiological disparity in disease burden between urban and rural areas, with rural areas having minimal pandemic preparedness and their own healthcare challenges. Therefore, this review aims to provide insight on the pathogenesis and the transmission dynamics of CoVID-19 along with pharmacological and non-pharmacological intervention strategies to mitigate the clinical manifestation of this virus. This review also aims to assess existing challenges of the CoVID-19 pandemic in rural areas based on past pandemic experiences and the effect on rural population. (2) Methods. A literature review was conducted using databases such as PubMed, Science Direct, Academic Search Premier, ProQuest, and Google Scholar, along with information from governmental organizations such as Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO). (3) Results. The causative virus, with its likely zoonotic origin, has demonstrated high pathogenicity in humans through increasing human-to-human transmission leading to extensive mitigation strategies, including patient quarantine and mass “social distancing” measures. Although the clinical manifestation of symptoms is mild in majority of the virus-inflicted population, critical patients may present with pneumonia and acute respiratory distress syndrome, exacerbated by pre-existing comorbidities, eventually leading to death. While effective coronavirus disease (CoVID-19)-specific vaccines and drugs are under clinical trials, several pharmacological and non-pharmacological interventions have been adapted to manage symptoms and curtail the effect of the virus to prevent increasing morbidity and mortality. Several persisting challenges have been noted for mitigating CoVID-19 in rural areas, including the poor healthcare infrastructure, health literacy, pandemic preparedness along with the fact that majority of rural population are frail subjects with pre-existing comorbidities. (4) Discussion. The increasing rate of incidence of CoVID-19 presents its own challenges, burdening healthcare institutions and the global economy, and impacting the physical and mental health of people worldwide. Given the clinical insights into CoVID-19 and the challenges presented in this review for the U.S. rural population, mitigation strategies should be designed accordingly to minimize the morbidity and mortality of this contagion.