The transition to Industry 4.0 and the introduction of new digital technology in industrial companies are evoking profound changes in their work systems. It is estimated that the emerging changes will affect both the overall performance of systems and the well-being of the humans working in and interacting with the systems. However, descriptive empirical evidence focusing on the pertaining effects of these emerging changes is minimal. Moreover, without the support of such empirical evidence, it will be challenging to provide prescriptive actions for how industrial companies might navigate through the transition to Industry 4.0. In this paper, we address this research gap and present empirical evidence collected through ten industrial case studies illustrating how the introduction of Industry 4.0-enabling technologies may affect human well-being and system performance before, during, and after implementation. Hereafter, we provide several implications and recommendations for practitioners. Relevance to industry: The results serve to assist organizational decision-makers, and Human Factors and Ergonomics experts with prescriptive guidelines and recommendations for dealing with and overcoming challenges related to human well-being and system performance in the transition to Industry 4.0.