While higher education has been considered as both an ‘engine’ for innovation and a ‘catalyst’ for sustainability development, the integration of both the ‘innovation engine’ and ‘sustainability catalyst’ roles is best reflected in higher education’s engagement in innovation ecosystems—the theme of this special issue, including 16 articles dealing with the topic from various perspectives. In this editorial, we outline an overarching framework about the relations between higher education and innovation ecosystem. When elaborating the framework, we provide a new definition of innovation ecosystem and identify three roles of university in innovation ecosystems, based on synthesizing relevant literature. The framework could facilitate readers to comprehend each of the collected articles and find synergy among them.