We conducted an assessment of maternal, newborn and child health and progress towards achieving Millennium Development Goals (MDG) 4 and 5 in the Eastern Mediterranean Region (EMR). We provide recommendations for scaling up and sustaining gains post-2015. Data were obtained from global data repositories. We constructed time trends from 1990 to 2013 and evaluated inequities across the Region. Under-5, neonatal and maternal mortality rates decreased 46%, 35%, and 50% respectively from 1990 to 2013. Pneumonia and diarrhoea accounted for 50% of all post-neonatal deaths; pregnancy- and delivery-related complications were the leading causes of neonatal and maternal deaths. Coverage of maternal, newborn and child health interventions is suboptimal, and poverty, food insecurity and conflict are pervasive across the Region. The EMR has made progress but is unlikely to attain MDG 4 and 5 targets. To sustain and further accelerate gains, the Region must reduce inequities and scale up implementation of recommendations made by the independent Expert Review Group.