Background: The Millennium Development Goal (MDG) period saw dramatic gains in health goals MDG 4 and MDG 5 for improving child and maternal health. However, many Muslim countries in the south Asian, Middle Eastern, and African regions lagged behind. In this study, we aimed to evaluate the status of, progress in, and key determinants of reproductive, maternal, newborn, child, and adolescent health in Muslim majority countries (MMCs). The specific objectives were to understand the current status and progress in reproductive, maternal, newborn, child, and adolescent health in MMCs, and the determinants of child survival among the least developed countries among the MMCs; to explore differences in outcomes and the key contextual determinants of health between MMCs and non-MMCs; and to understand the health service coverage and contextual determinants that differ between best and poor or moderate performing MMCs. Methods: In this country-level ecological study, we examined data from between 1990 and 2015 from multiple publicly available data repositories. We examined 47 MMCs, of which 26 were among the 75 high-burden Countdown to 2015 countries. These 26 MMCs were compared with 48 non-Muslim Countdown countries. We also examined characteristics of the eight best performing MMCs that had accelerated improvement in child survival (ie, that reached their MDG 4 targets). We estimated adolescent, maternal, under-5, and newborn mortality, and stillbirths, and the causes of death, essential interventions coverage, and contextual determinants for all MMCs and comparative groups using standardised methods. We also did a hierarchical multivariable analysis of determinants of under-5 mortality and newborn mortality in low-income and middle-income MMCs. Findings: Despite notable reductions between 1990 and 2015, MMCs compared with a global esimate of all countries including MMCs had higher mortality rates, and MMCs relative to non-MMCs within Countdown countries also performed worse. Coverage of essential interventions across the continuum of care was on average lower among MMCs, especially for indicators of reproductive health, prenatal care, delivery, and labour, and childhood vaccines. Outcomes within MMCs for mortality and many reproductive, maternal, newborn, child, and adolescent health indicators varied considerably. Structural and contextual factors, especially state governance, conflict, and women and girl's empowerment indicators, were significantly worse in MMCs compared with non-MMCs within the high-burden Countdown countries, and were shown to be strongly associated with child and newborn mortality within low-income and middle-income MMCs. In adjusted hierarchical models, among other factors, under-5 mortality in MMCs increased with more refugees originating from a country (β=23·67, p=0·0116), and decreased with better political stability or absence of terrorism (β=–0·99, p=0·0285), greater political rights or government effectiveness (β=–1·17, p<0·0001), improvements in log gross national income per capita (β=–4·44, p<0·0001), higher total adult literacy (β=–1·69, p<0·0001), higher female adult literacy (β=–0·97, p<0·0001), and greater female to male enrolment in secondary school (β=–16·1, p<0·0001). The best performing MMCs were Azerbaijan, Bangladesh, Egypt, Indonesia, Kyrgyzstan, Morocco, Niger, and Senegal, which had higher coverage of family planning interventions and newborn or child vaccinations, and excelled in many of the above contextual determinants when compared with moderate or poorly performing MMCs. Interpretation: The status and progress in reproductive, maternal, newborn, child, and adolescent health is heterogeneous among MMCs, with little indication that religion and its practice affects outcomes systemically. Some Islamic countries such as Niger and Bangladesh have made great progress, despite poverty. Key findings from this study have policy and programmatic implications that could be prioritised by national heads of state and policy makers, development partners, funders, and the Organization of the Islamic Cooperation to scale up and improve these health outcomes in Muslim countries in the post-2015 era. Funding: US Fund for UNICEF under the Countdown to 2015 for Maternal, Newborn, and Child Survival, the Centre for Global Child Health, Hospital for Sick Children, and the Aga Khan University.