During the last 20 years, social and political consensus has afforded the successful gradual implementation of entrepreneurship policy in Chile, transforming the country into one of the world’s most productive entrepreneurship ecosystems. However, the excessive political and economic centralization that has characterized Chile raises the question of whether spatial dependence influences entrepreneurship and what factors have led to this condition. By applying spatial econometric tools to data from 320 districts in Chile during the period 2013–2014, we conclude that there is spatial dependence among districts in Chile in relation to the creation of new businesses and that the immigrant population, the presence of different categories of universities and local patenting capacity are the variables with the greatest positive effect on this dependence.