Despite the rapid decline of childhood mortality in Nepal, there is considerable variation in the rate of progress by ecological region. Using the Nepal Demographic Health Survey 2011 data, we investigate two critical questions: first, whether the ecological differences in childhood mortality still remain independent of the factors known to influence mortality and second, what socio‐economic and demographic factors shape these differences in childhood mortality across the ecological regions? The results from the Cox proportional hazard regression analysis, which controls for established socio‐economic and demographic factors known to influence childhood mortality, suggest that children who live in the hill and the Terai regions have a lower probability of death than those from the mountainous areas. The results of the Blinder–Oaxaca decomposition model further reveal that father's education, household economic status, place of residence, higher‐order births with lower birth interval, and mother's employment status significantly contribute to differences in childhood mortality across the ecological regions. Our findings provide important insights on the issue of (ecological) regional disparities in childhood mortality and draw attention to critical challenges for socio‐economic, population, and health policy in Nepal. Copyright © 2015 John Wiley & Sons, Ltd.