COVID-19 has proven to be detrimental across the globe, most notably affecting the United States at an alarming rate compared to comparable countries. The pandemic has had multifactorial implications on the way communities in the United States prevent, prepare for, and address the virus; however, the impact of the pandemic on rural health is less well understood. Historically, rural communities have faced a unique set of challenges regarding accessing and receiving adequate healthcare, addressing chronic illness, and eliminating health disparities closely associated with the population’s socioeconomic status; the pandemic has exacerbated these challenges. The purpose of the current study was to conduct a systematic review of the literature to evaluate the effect of the COVID-19 pandemic on rural populations both at the individual and community level. Results indicated that rural health disparities increased both at the individual and system-wide levels as a direct result of the pandemic. Budget cuts significantly affected the infrastructure of rural hospitals resulting in them being unequipped to handle such high volumes of COVID-19 cases. The lack of infectious disease specialists, access to larger medical centers with substantial numbers of ICU beds and ventilators, and an overall lack of preparedness overwhelmed rural communities. Although comorbidities such as diabetes and heart disease were associated with poorer health outcomes for a multitude of reasons, the lack of clinic and physician availability for routine care during the pandemic further exacerbated the clinical link from COVID-19 positivity to comorbidities. Furthermore, mental health deteriorated as substance use increased to a greater extent in rural communities compared to urban, during the pandemic. This study shows that health comorbidities, mental health, substance use, health literacy, access to healthcare, among others can serve as key indicators for improving healthcare in rural communities. Future studies should seek to identify key issues that disproportionately affected rural communities in comparison to their urban counterparts considering the pandemic, as well as identify gaps in the availability of rural health resources that can improve the lives of millions of Americans now and during the next pandemic.