Zoonotic diseases continue to affect the health and livelihood of resource limited communities. In Ethiopia, despite the presence of a national master plan for prevention, control and elimination of some common zoonotic diseases, well-organized epidemiological data regarding incidence and distribution are lacking. A retrospective cross-sectional study based on a patient medical data recorded from 2012-2016 in selected districts of Southern Tigray, North Wollo zone of Amhara region and Ab'Ala district of Afar region was conducted to map the distribution and Incidence proportion of major zoonotic diseases. The incidence proportion of four major zoonotic diseases (helminthiasis, tuberculosis (TB), rabies and schistosomiasis) was mapped using qGIS software based on the Health Management Information System (HMIS) data collected from district health facilities. The result indicated that, out of a total 1,273,145 observed human disease cases, 53,614 (4.2%) of them were potential zoonotic diseases that include: helminthiasis (51,192), TB (2,085), rabies (227), schistosomiasis (105) and visceral leishmaniasis (7). The highest incidence proportion of TB (262.8 cases per 100,000 population) and rabies (33.2 cases per 100,000 population) were recorded in Gubalafto and Weldya followed by Raya Alamata (253.4 cases per 100,000 population %), and Ab'Ala and Raya Azebo (29 cases each per 100,000 population) for TB and rabies, respectively. The highest incidence proportion for schistosomiasis was reported in Raya Alamata (50.1 cases per 100,000 population) followed by Gubalafto and Weldya (10.8 cases per 100,000 population). The incidence proportion of visceral leishmaniasis per 100,000 population was 4.1, 1.3 and 1.2 cases for Ab'Ala, Gubalafto and Weldiya, and Raya Azebo districts, respectively. Except rabies, which showed high incidence proportion (p<0.0001) in 5-14 age groups, the other zoonotic diseases showed higher incidence proportion (p<0.0001) in age groups above 15 years. Rabies, helminthiasis and schistosomiasis showed statistically significant variation (p<0.0001) among seasons. Rabies and TB showed decreasing trend within the data recorded years. In animals, only 31 rabies cases and 15 anthrax cases were recorded from 2012 to 2016. This finding highlighted the distribution and incidence of some major zoonotic diseases in the study areas. Systematic and detailed research should be conducted in the future to map the distribution of major zoonotic diseases at regional and country level so as to initiate integrated effort from human and animal health authorities and professionals.