Abstract 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.