Background. Mismanagement of healthcare waste (HCW) during the COVID-19 pandemic can facilitate the transmission of coronavirus. Regarding this problem, there is gap of evidence in Ethiopia, and this study aimed to assess the HCW generation rate and management in Tepi General Hospital, southwest Ethiopia. Methods. Institution-based cross-sectional and case studies were conducted. The total amount of waste generated and its type among various case teams were compared using the Kruskal–Wallis test. Spearman’s rank correlation coefficient (r) was used to assess the correlation between the total numbers of patients and the total amount of HCW generated. Qualitative data were transcribed verbatim, translated to English, and analyzed with Open Code version 4.02 software, and content analysis was followed. Results. The total mean weight (±SD) of waste generation rate in all service units of the hospital was 492.5 ± 11.5 kg/day. The higher proportion (61.9%) of the total HCW produced was general waste and the remaining (38.1%) was hazardous waste. There was a statistically significant (X2 = 82.1,
p
<
0.001
) difference in daily HCW generation rate among different case teams. Similarly, the hospital waste generation amount and total patient flow had a strong positive linear relationship (r = 0.7,
p
=
0.032
). COVID-19-related medical wastes were not properly handled, segregated, stored, and disposed. There was a scarcity of resources needed to manage HCW, and available resources were utilized poorly. Overall, healthcare wastes were managed as usual (pre-COVID-19). Conclusion. The mean HCW generation rate in Tepi General Hospital was high. Overall, wastes were mismanaged, and COVID-19-related HCWs have been managed as usual. Availing of important resources and training the concerned bodies should be considered during the crisis of COVID-19.