Climate change and variability is causing the greatest environmental, social and economic threats to all countries across the world; however, the problem is severe to many developing countries including Ethiopia emanated from their weak adaptive strategies. This study intends to assess farmers perception, vulnerability, adaptation strategies used and the determinants that hinder to cope up to climate change and variability in North Mecha district, Amhara Region, Ethiopia. The study employed both quantitative and qualitative approaches. Primary data for the study were collected through questionnaire from 138 respondents, focus group discussion, key informant interviews and field observation selected through stratified random sampling technique based on agro-ecology. Secondary data were collected from NASA power. LVI and LVI-IPCC methods were used to assess farmers vulnerability to climate change and variability using SPSS version 26. Descriptive statistics are used to characterize perception and dummy variables and to compare them using the chisquare test. The statistical data was entered and analyzed using SPSS version 26. The overall vulnerability result in the case of LVI is 0.394 and 0.382 for Woyna Dega and Dega agroecological zones respectively. Similar result was found using the LVI-IPCC approach which was 0.051 for Woyna Dega and 0.019 for Dega agro-ecology. Both LVI and LVI-IPCC results revealed that Woyna Dega was greater vulnerable to climate change and variability than Dega agro-ecology. The LVI-IPCC also implied that households of Woyna Dega were more exposed, relatively more sensitive and relatively less adaptive capacity to climate change and variability than Dega agro-ecology. The results revealed significant increasing trend in annual average temperature and decrease annual rainfall trend as well as a higher rainfall variability. Similarly, 75.4% and 73.9% of the interviewed households were aware of an increase in temperature and a decrease in rainfall respectively. The multiple response model results revealed that the main adaptation strategies of farmers include soil and water conservation, use improved variety, planting tree, water harvesting and irrigation. Binary logistic model revealed determinant factors such as gender, age, family size, educational status, farming experience, access to extension service, access to climate information, lack of infrastructure, farmland size and financial problem which has a positive and negative impact on different adaptation strategies used by farmers in the district. The findings can be used by the government of Ethiopia reduce vulnerability and enhance adaptive capacity of both agro-ecologies. In addition, income and livelihood diversification may be one of the options to reduce vulnerability in both agro-ecologies of the study area.