Entrepreneurship usually takes place in innovative systems, mostly in cities. Cities, with unique features, may alter the impact of entrepreneurship. This paper employs multiple regression models to assess the impact of entrepreneurship on economic growth, considering the moderation effect of the city context. We use Gross Domestic Product (GDP) as the dependent variable and government spending, labor, fixed and financial capital and entrepreneurship as the independent variables. The data are from the 2003–2017 yearbooks of Zhaoqing, Shantou and Meizhou (three cities with distinct cultural and geographic features in Guangdong, China). We conclude that (1) the three cities’ GDPs highly rely on traditional factors of production (i.e., government spending, labor and fixed and financial capital) rather than entrepreneurship and (2) the city context of Meizhou is relatively unsupportive of its entrepreneurship contributing to the GDP, in comparison with that of Zhaoqing and Shantou. This study adds to the literature by empirically assessing and comparing three cities’ entrepreneurship development in China; it also informs scholars and practitioners of the moderation effect of the city context.