Background Disability influences activities of daily living, leading to unsafe conditions, poor quality of life, and dependence on others and assistive technologies. Despite limited access and unmet needs, assistive technology enables users to participate in education and be independent members of their community. Students with disabilities in higher education face many challenges in their day-to-day activities and evidence is limited in the study area. Therefore, this study aimed to explore assistive technology experience and daily living challenges among students with disabilities in higher education. Method A descriptive qualitative study design was employed at the University of Gondar, Gondar, Ethiopia, between December 20, 2022, and January 20, 2023. A purposive sampling method was employed to recruit 14 students with disabilities. An in-depth interview was employed using semi-structured questionnaires. Open Code version 4 software for coding and reflexive thematic analysis approach was employed for the analysis. Result A total of 14 students with disabilities were included in an in-depth interview. Four main themes emerged, which included activities of daily living, attitudes toward people with disabilities, barriers to accessibility, and access to assistive technology. Conclusion Barriers to activities of daily living among students with disabilities were poor accessibility of infrastructural facilities, lack of teaching/learning materials in an accessible format, and negative attitudes. The present study’s finding is needed to support students in higher education for their academic achievement and to design appropriate rehabilitation strategies and policies on the accessibility of physical infrastructures, inclusive education, and the provision of assistive technology