The purpose of the present study is to explore challenges faced by classroom teachers in multi-grade classes from a comparative perspective of pre-pandemic and peri-pandemic processes. The qualitative case study was employed as the research design. Nine classroom teachers working in multi-grade classes in a district of southeastern Turkey were recruited using the criterion-based sampling technique. Three focus group interviewing sessions, three teachers in each session, were carried out to gather data. The researchers utilized a semi-structured interview protocol including eight open-ended questions. Data were analyzed using thematic analysis. The themes produced were categorized as challenges before the pandemic, challenges faced in distance education during the pandemic, and challenges faced in face-to-face education during the pandemic. The challenges accentuated most, in the pre-and peri-pandemic periods, were parents’ indifference, students’ approaches to learning, inappropriate learning materials, frequent electric and water outages, a lack of internet infrastructure, difficulties to ensure social distancing in the classroom, and difficulties to teaching under the pandemic conditions