Uganda’s formal education system, rooted in colonial paradigms, continues to produce graduates oriented towards employment rather than enterprise creation. Despite over a century of educational evolution, the underlying philosophy has not sufficiently shifted to cultivate innovation, entrepreneurship, and start-up ecosystems essential for economic transformation. Yet, while existing studies have highlighted the absence of a coherent educational philosophy in Uganda, few have critically examined how this philosophical vacuum specifically constrains the development of innovative and entrepreneurial graduates. This paper addresses that gap by examining how Uganda’s educational philosophy can be reimagined to foster innovation-driven and entrepreneurial mindsets in higher education. The study identified the philosophical foundations underpinning Uganda’s higher education, and assessed how the available philosophy enabled and constrained conditions for fostering innovation, entrepreneurship, and start-up ecosystems. Using the qualitative approach, the study adopted a descriptive and explanatory design. Data was collected from a sample of eight key informants (KIs), three in-depth interviews (IDIs), and two focus group discussions (FGDs). The two FGDs comprised university lecturers (UCU–Mbale Campus) and teacher trainees (Gulu University). Participants were drawn from the Ministry of Education and Sports (MoES), NCHE, research organisations, and among educationists and university professors, representing university administrators, policymakers, professors of education and philosophy, education research organisations, university lecturers, and teacher trainees. Higher education stakeholders across four regions of Uganda were consulted in 2022. The reflective interview guides were administered and analysed thematically with descriptive and analytical methods. The study found that the country lacks a coherent, explicitly articulated educational philosophy and instead operates with an amalgam of competing philosophical orientations. We argue that this philosophical fragmentation, inherited from colonial educational models that emphasised passive knowledge consumption overactive knowledge creation, fundamentally constrains graduates’ capacity to innovate and establish enterprises. The paper contributes to the ongoing discourse on educational reform by offering a contextual framework for embedding innovation and entrepreneurship within Uganda’s higher education philosophy, ultimately supporting the development of sustainable start-up ecosystems that address local challenges while connecting to global opportunities.