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In response to the impending spread of COVID-19, universities worldwide abruptly stopped face-to-face teaching and switched to technology-mediated teaching. As a result, the use of technology in the learning processes of students of different disciplines became essential and the only way to teach, communicate and collaborate for months. In this crisis context, we conducted a longitudinal study in four German universities, in which we collected a total of 875 responses from students of information systems and music and arts at four points in time during the spring–summer 2020 semester. Our study focused on (1) the students’ acceptance of technology-mediated learning, (2) any change in this acceptance during the semester and (3) the differences in acceptance between the two disciplines. We applied the Technology Acceptance Model and were able to validate it for the extreme situation of the COVID-19 pandemic. We extended the model with three new variables (time flexibility, learning flexibility and social isolation) that influenced the construct of perceived usefulness. Furthermore, we detected differences between the disciplines and over time. In this paper, we present and discuss our study’s results and derive short- and long-term implications for science and practice.