In economic literature, the relationship between entrepreneurship and economic growth has been widely discussed for some time now. In addition to the different theoretical approaches, a considerable amount of empirical works in recent decades have sought to verify the direct link between both variables by analyzing datasets from several distinct geographic areas. On one hand, it highlights the absence of a common indicator to measure entrepreneurship in practice relating to a country’s economic growth; on the other hand, it shows a great diversity of factors determining them. With the aim of providing new empirical evidence in the field of European entrepreneurship, this paper has analyzed data relating to 31 European countries over the last decade by introducing self-employment as an empirical proxy of entrepreneurship. In particular, this study contrasts the positive effect of public expenditure, investment, human capital, and entrepreneurship on economic growth for a wide range of countries and examines the impact of some economic and educational variables on self-employment, such as unemployment, taxes, education, and early school leaving. The estimation method used in this research had to consider the Ordinary Least Squares through a multiple regression model of constant coefficients based on annual Eurostat statistics for the period of 2010 to 2019. The results obtained verify the positive effect of public expenditure, investment, human capital, and entrepreneurship on economic growth. Moreover, the analysis of other factors affecting entrepreneurship, segregated by gender, shows how unemployment and the level of education have a positive impact on self-employment, while significant increases in the tax rate on capital and early school leaving harmed such variable. No significant differences were found between males and females.