Social entrepreneurship (SE) incorporates the more ethical dimensions of innovative business practices in the pursuit of financial sustainability in the advancement of societal goals, and is intended to empower all participants while bringing about positive changes in communities and society at large. An increasing number of colleges and universities are now embracing SE to stay competitive in the higher education market, find new sources of income in times of fiscal constraint, and align with their public service missions. However, despite the interest in SE on the part of the academic community, there is no broad or consistent understanding regarding what actually constitutes SE in higher education settings (SEHE), or about how it is being carried out in the institutions that have adopted SEHE. A multi-case study design explores a proposed initial SEHE framework developed from the literature through a qualitative analysis of the experiences of five higher education institutions recognized for their adoption of SE practices. This qualitative approach utilizing the lens of structuration theory enables the development of a complex understanding of SEHE as a multifaceted social phenomenon derived through the examination of its actors in their structural context. The revised SIEHE framework, informed by the experiences of these exemplar institutions, is intended both to advance scholarly understanding of the elements and process of SIEHE, and to serve as a model for those undertaking or considering SE implementations at other colleges and universities. The framework sheds new light on the definitional and operational aspects of SE, and translates concepts that have previously been largely confined to the business literature to other disciplines, enabling their adoption by scholars and practitioners in such diverse areas as education, the social sciences, and the liberal arts. While allowing for a broader scope of the types of socially beneficial projects that could be undertaken by agents, including faculty from a larger range of disciplines, SIEHE’s emphasis on financial sustainability should also be attractive to administrations for enabling access to alternative funding sources.