Measures of entrepreneurship, such as average establishment size and the prevalence of start-ups, correlate strongly with employment growth across and within urban areas. Is it possible for entrepreneurship to occur outside of urban areas and be active in rural areas such as Ohio, Pennsylvania, and West Virginia? There are causal links of entrepreneurial finance to industry or city growth but little link of the evidence of entrepreneurship outside of urban areas overall. This chapter examines the regional variation in startup concentration used to predict employment in the rural areas of Pennsylvania, Ohio, and West Virginia by metropolitan statistical area (MSA)/micropolitan areas for the year 2017. The authors find significant differences in new firm formation rates from industrial regions to technologically progressive regions using the generalized linear models (GLM). Variations in firm birth rates are explained by industrial size, population growth, the number of startups, human capital variables, and establishments.