A cross-sectional and longitudinal observational study with the objectives to identify calf management and husbandry practices and to investigate the major causes of calf morbidity and mortality and its associated risk factors was conducted in South Omo Zone from 2015 to 2016. A total of 85 calf owners were interviewed and 255 calves of those farmers were longitudinally followed for six months from the very first day of their birth. Accordingly, retained placenta 17/85 (20%), narrow pelvic outlet 17/85 (17.6%) and prolonged labour 8/85 (9.4%) were ranked as maternal-related calving problems whereas, ‘navel ill’ 34/85 (40.0%), dead birth 9/85 (10.6%), oversized calve 16/85 (18.8%) and abnormal presentation 9/85 (10.6%) were identified as calf-related problems. The traditional healers 31/85 (36.47%) and veterinarians 24/85 (28.23%) were dominant calving assistants in the study areas. Moreover, bloody diarrhea 24/85 (28.2%), ectoparasites 10/85 (11.8%), pneumonia 7/85 (8.2%) and constipation 3/85 (3.5%) were categorized as the major health problems that frequently affected the calves. From the calves longitudinally followed, 85 calves (33.3%) were encountered different health problems which resulted in calf morbidity and mortality. Identified health problems were not significantly associated (p>0.05) with study sites, sex and breed of calves. According to multiple logistic regression analysis, six variables (calf housing system, dam vaccination history, colostrum feeding frequency, calf house clearing frequency, parity of the dam and calf delivery problem) were significantly associated (p<0.05) with calf morbidity. However, none of the variables was significantly associated with calf mortality. Through six months follow-up, 4.41% crude calf mortality rate was recorded. Sudden death with unknown cause, bloody diarrhea, pneumonia, “evil eye” and physical damages were responsible for 36.36, 18.18, 18.18, 9.09 and 18.18% case fatality and responsible for 1.60, 0.80, 0.80, 0.40 and 0.80% crude mortality respectively. The crude mortality varies among sex; 3.13 and 6.67% respectively in male and female calves. Similarly, it was relatively higher in calves under one week of age (5.73%) and decreasing as the calf’s age increased. It can be concluded that improving herd management and husbandry practices which negatively affecting calf health could minimize calf morbidity and mortality. Moreover, improving the whole herd health system and awareness creation to calve owners to improve the dynamism of their future replacement calve is very important in this area.