The study analyzed the level of agro-ecosystem sensitivity to climate change among the agro-climatic zones (ACZs) that are situated in the highlands of Lake Tana sub-basin. The analyses considered the actual land capability class (LCC in % considering soil texture, slope and elevation zone), crop diversity (count), length of growing period (LGP, month), and inter-annual variability of climate (mean annual rainfall-MARF in mm, mean monthly minimum temperature-MMMinT in ºC, and mean monthly maximum temperature-MMMaxT in ºC). For comparison purpose, it was essential to index/standardize the values of specified indicators. The proportion of arable land varied from 13.30% (in the Sub-Alpine) to 93.00% (in the Moist-Cold). The value of coefficient of variation showed the presence of variations of 7.85-11.21 (%), 7.21-10.34 (%), 16.37-39.61 (%) for MARF (mm), MMMaxT (ºC), and MMMinT (ºC), respectively across the ACZs. The inter-annual variability of both onset and offset time of rainy season was found to be in the range of 0.3-1.25 months. The LGP (month) was in the range of 3.25-6.25 across the ACZs; whereas crop diversity (count) ranged from 2-7. The production of red onion (allium cepa), oat (Avena sativa), local wheat (Triticum), and pea (Pisum sativum) was abandoned in the Sub--Alpine; whereas the production of linseed (Linmu usitatisimum), barley (Hordeum vulgare), and niger (Guizotia abyssinica) in the Moist-Cool. Yet, crops like maize and tef became the common crops in the Cold, possibly because of global warming. The indexed value of agro-ecosystem sensitivity to climate change ranged from 0.14-0.71. The level of agro-ecosystem sensitivity was higher towards the Sub-Alpine. The local development interventions to be made in the various ACZs need to be determined/prioritized considering the level of agro--ecosystem sensitivity.