Ethiopia is one of the sub-Saharan African countries contributing to the highest number of maternal and neonatal deaths. Coverage of maternal and neonatal health (MNH) interventions has remained very low in Ethiopia. We examined the cost-effectiveness of selected MNH interventions in an Ethiopian setting. We analysed 13 case management and preventive MNH interventions. For all interventions, we used an ingredients-based approach for cost estimation. We employed a static life table model to estimate the health impact of a 20% increase in intervention coverage relative to the baseline. We used disability-adjusted life years (DALYs) as the health outcome measure while costs were expressed in 2018 US$. Analyses were based on local epidemiological, demographic and cost data when available. Our finding shows that 12 out of the 13 interventions included in our analysis were highly cost-effective. Interventions targeting newborns such as neonatal resuscitation (institutional), kangaroo mother care and management of newborn sepsis with injectable antibiotics were the most cost-effective interventions with incremental cost-effectiveness ratios of US$7, US$8 and US$17 per DALY averted, respectively. Obstetric interventions (induction of labour, active management of third stage of labour, management of pre-eclampsia/eclampsia and maternal sepsis, syphilis treatment and tetanus toxoid during pregnancy) and safe abortion cost between US$100 and US$300 per DALY averted. Calcium supplementation for pre-eclampsia and eclampsia prevention was the least cost-effective, with a cost per DALY of about US$3100. Many of the MNH interventions analysed were highly cost-effective, and this evidence can inform the ongoing essential health services package revision in Ethiopia. Our analysis also shows that calcium supplementation does not appear to be cost-effective in our setting.