The education system is one of the sectors that have been severely affected by COVID-19. As a result, a new way of teaching-learning was initiated by world’s educational institutions to try to educate their students through online learning platforms. Hence, this study aims at exploring barriers and enablers of online education as well as the psychosocial well-being of university students during COVID-19 in eastern Ethiopia with a particular focus on Haramaya University. A concurrent mixed method design was employed. A total of 384 participants were selected using a stratified random sampling technique. Questionnaires, key informant interviews, and document analyses were used to collect data. Quantitative data were analyzed using descriptive statistics and qualitative data were analyzed thematically, then the analyzed data were integrated to get a holistic picture of the study result. The study revealed that university students experienced high levels of barriers, low levels of enablers, and severe levels of psychosocial problems while attending their education online during the COVID-19 pandemic. Hence, proactive measures taken for identifying and removing barriers, enhancing enablers, and creating a support system that shields the psychosocial well-being of university students are recommended as appropriate intervention strategies to adapt the online education modality in universities during the COVID-19 pandemic.