This paper examines two core issues of the university-based entrepreneurship education ecosystem by explicating the key elements of the ecosystem and their roles, and the development process and sustainable construction strategy of the ecosystem. Thirty stakeholders of ecosystems from the US universities were interviewed, and the transcripts of these interviews were coded through a three-phase process, including open, axial, selective coding, and were analyzed based on the grounded theory. It was found that (i) the key elements of the university-based entrepreneurship education ecosystem consist of six units (colleges and universities, learners, educators, government, industry, and community) acting as initiators and seven factors (entrepreneurship curriculum, entrepreneurial activities and practices, organizational structure, resources, leadership vision, core faculty, and operating mechanism) acting as the intermediaries; (ii) These key elements constitute three independent functional subsystems, namely, teaching and innovation, support, and operation that are interconnected by the universities; (iii) The development process of a university-based entrepreneurship education ecosystem involves seven steps as preparation, germination, growth, equilibrium, stagnation, recession, and collapse; (iv) For sustainability, suggestions on a solid foundation, continuous investment, and constant monitoring are provided to university administrators and policymakers to advance higher education’s contribution to social and economic development.