This work proposes a line of innovation to implement possible uses for the e-portfolio in higher education. We present an initial framework for analysis with attention to three main arguments: the validity of the interest of the e-portfolio for higher education in light of the current challenges posed by the knowledge society; the relevance of complex change management within organisations such as universities; and the identification of critical elements in the relevant literature concerning experiences similar to the case analysed here. The milestones for the line of innovation include six projects and three teacher training courses. Once data had been gathered in the respective assessment phases for each milestone by means of document analysis techniques (e-portfolios, teaching materials, usage statistics), questionnaires, discussion groups, in-depth interviews, and self-assessments (responsible academics, teachers, and students), a global analysis of the whole line was conducted from a complex approach to the problems of teaching change and innovation. A technological, political and cultural reading of innovation reveals emerging problems to reconsider: the attainment of deep learning; the standardisation of academic tutoring; the formation of learning and practice communities; the reconceptualisation of the e-portfolio as a personal learning environment; and the transformation of the university institution as a learning organisation. The premature condition of higher education to deal with the change in the teaching paradigm and the urgency to revisit its innovation policies to overcome it stand out among the critical conclusions of this study.