Background Globally, neonatal and child mortality remains still high. Under-five mortality accounts for four-fifth of child and young adolescent deaths. In Ethiopia, though there has been a remarkable progress over the past years, under-five mortality is still high. Evidence from population-based longitudinal studies on under-five mortality is limited. Thus, this study aims to investigate the magnitude, trend, and causes of under-five mortality in the Kilite-Awlaelo Health Demographic Surveillance System, Northern Ethiopia. Methods Kilite-Awlaelo health and demographic surveillance system was established in 2009 in the northern part of Ethiopia. Population-based longitudinal study design was carried out through extracting data for nine consecutive years (2009–2017). After smoothing the data revealed a visually decreasing trend. Linear, quadratic, exponential, and autoregressive time-series models were checked. Accordingly, the exponential trend model provided the best fit with the lowest standard error of estimate, lowest sum square error and highest adjusted R2 value. Cause-specific mortality was determined by cross tabulating cause of death with specific age death. Results The overall under-five mortality rate was 35.62 per 1000 livebirths. The under-five mortality rate of rural and urban residents was 37.58 and 12.99 deaths per 1000 livebirths respectively. The exponential trend model showed the under-five mortality rate was declining exponentially. Bacterial sepsis 67(20.6%), prematurity 37(11.08%), intestinal infection disease 30(8.98%), acute lower respiratory infections 26(7.78%), and birth asphyxia 24(7.19%) were the major causes of under-five mortality. Conclusion The overall under-five mortality rate for the surveillance period was comparatively lower. A statistically significant difference in under-five mortality rate was observed between urban and rural residents. A statistically significant declining trend in the under-five mortality rate was observed. Bacterial sepsis, prematurity, intestinal infection disease, acute lower respiratory infections, and birth asphyxia were the major causes of under-five mortality. We recommend the huge discrepancy in under-five mortality rate between urban and rural dwellers could be narrowed to some level by increasing healthcare access for rural residents.