A questionnaire based herd level cross-sectional survey followed by calf level longitudinal prospective study design was carried out between February 2022 and August 2022 on calf morbidity and mortality in mixed crop-livestock production system in South and North Achefer Districts of West Gojjam Zone, Northwestern Ethiopia. The objective of this study were to: i) explore calf health problems and farm management practices, ii) quantify the incidence and identify predictors and causes of calf morbidity and mortality, and iii) quantify the economic losses of calf morbidity and mortality in the study areas. A total of 231 pre-weaning calves from 231 dairy cattle producers were considered for the study. Logistic regression was employed to examine and quantify herd level risk factors affecting the occurrence of calf morbidity and mortality in surveyed farms. Whereas Kaplan-Meier (K-M) method and Cox proportional hazards regression were used to summarize the cumulative survival and to identify and quantify factors affecting calf morbidity and mortality from birth to 210 days of age. Survey findings revealed that about 30.7% and 15.2% of respondents had experienced calf morbidity and mortality in the past one year. These were significantly (p<0.05) influenced by calf attendant’s farm experience and training background. Among 231 calves enrolled for the prospective cohort study, a total of 84 morbidity and 17 mortality events were recorded. This gives an overall morbidity and mortality incidence rates (IRs) of 57 per 100-calf seven- months at risk (risk rate of 43.4%) and 8 per 100-calf seven months at risk (risk rate of 7.7%), respectively, or conversely, the overall seven months cumulative survival rate of calves from morbidity and mortality was 61.5% and 90.5%, respectively. The most commonly diagnosed disease syndrome was diarrhea with risk rate of 14%, followed by septicemia (7.7%), nevertheless, septicemia was the leading cause of calf death (3.5% of 17 calf death, followed by diarrhea (1.3% of all 17calf deaths). Calf vigor status at birth, calf breed, calf house hygiene and colostrum ingestion were found significant (p<0.05) predictors of calf morbidity from birth to seven months of age. Whereas calf breed, vigor status at birth, calf house hygiene and ventilation status, mothering instinct and dam parity were found significantly (p<0.05) predictors of crude mortality. The overall estimated economic losses due to calf morbidity (84 sick calves) and mortality (17 calf deaths) during the study period were 9,240.00 ETB (175.7US$) and 586,619.00 ETB (11,152.45US$) respectively, which is equivalent to the financial losses of 110 ETB (2.09US$) due to morbidity and 34,617 ETB (658.1 US$) due to mortality at household level. Specifically, the overall financial loss due to mortality, milk yield loss and morbidity including (weight losses) were 586, 619.00 ETB (11,152.45 US$),307,989 ETB (5855.3US$) and 10,635 ETB (202.2US$), respectively. In conclusion, a relatively higher level of calf morbidity and mortality with multitude herd and calf level risk factors were investigated in the study areas. This could negatively affect the replacement stock and income of cattle producers, where cattle production was an integral component of livestock agriculture in the study areas. Therefore, a targeted intervention centered on mitigating the identified herd and calf level risk factors is warranted. Besides, further comprehensive study using proper economic analysis is suggested to investigate the long-term impact of calf morbidity and mortality on the productivity performance of individual animal and farm level economic performances.