Unemployment is rising in Africa due to inefficient economic performance; rural –urban migration as well as the speeding up poverty. Ethiopia is not exceptional in facing by such daunting unemployment and poverty and its resultant effect at both the rural and urban areas. Government envisaged and implemented national economic policies and programs, for instance, micro and small enterprise and technical and vocational training programs that boost local and small business growth in the urban areas. Micro and small enterprise particularly local and small business activities created vast job opportunities in cities in Amhara regional state, specific to South Wollo and Oromiya administration Zone, Ethiopia. However, local and small business were in fact triggered and faced by adverse factors, COVID-19 was prevalently affecting their monthly sale, saving, expenditure and overall activities. Along with this, this study pinpointed the effect of COVID-19 on the local and small businesses activities in Kemissie, Dessie, Kombolecha and Haik. In pursuit of it, this study employed a descriptive type of research design using cross sectional surveyed data. In pursuit of this, binary logistic regression model and stata software 14 version was used to determine significant effect of COVID-19 on local and small business. Along with this, this study, identified that COVID-19 was influenced the local and small business owner’s income; saving and expenditure. Moreover, lack of loan without collateral and working area were significantly affecting local and small business activities besides to the COVID-19 lockdown. This, study, therefore, suggest to whom it may concern to subsidies and deliver loan without collateral; entrepreneurial and client handling training, working areas for local and small business that will have help of resilienting from the effect of COVID-19 pandemic and the rising inflation effect in the study area and at large in Amhara region, Ethiopia.