Background: Rate and pattern of under-five mortality is a reflection of a society’s healthcare system and quality of life. This study is aimed at reviewing the causes of infants and under-five morbidity and mortality in Calabar, Southern Nigeria. Methods: This study used retrospective descriptive cross-sectional design. We did a retrospective collation of data on under-five morbidity and mortality from 2012 to 2017 of under-five patients admitted or died while in admission in University of Calabar Teaching Hospital. The causes of morbidity and mortality were reported based on International Classification of Diseases 10 (ICD-10). The morbidity, mortality and fatality rates were computed. Results: A total of 11,416 under-five admissions and 391 deaths were recorded within the study period giving a fatality rate of 3.4%. Age 1–4 years category represented 50.5% of the admissions while infants (<1 year) constitute majority of the deaths (64.7%). There were 5652 infant admissions and 253 infant deaths giving fatality rate of 4.5% within the study period. Males constituted majority (55.8%) of under-five morbidity whereas females constituted majority (51.2%) of the deaths. Conditions originating from perinatal period; and infectious and parasitic diseases were the leading broad cause of under-five mortality. Specific disease analysis showed sepsis/septicemia; congenital infectious and parasitic diseases; slow fetal growth, malnutrition and short gestation as the chief causes of both infant and under-five mortality. Conclusion: The leading causes of under-five deaths in the studied population are amenable. Improved healthcare and antenatal will be of immense benefit.