Summary Background After the fall of the Taliban in 2001, Afghanistan experienced a tumultuous period of democracy overshadowed by conflict, widespread insurgency, and an inflow of development assistance. Although there have been several cross-sectional assessments of health gains over the last decade, there has been no systematic analysis of progress and factors influencing maternal and child health in Afghanistan. Methods We undertook a comprehensive, systematic assessment of reproductive, maternal, newborn, and child health in Afghanistan over the last decade. Given the paucity of high-quality data before 2001, we relied mainly on 11 nationally representative surveys conducted between 2003 and 2013. We estimated national and subnational time trends for key reproductive, maternal, and child health indicators, and used linear regression methods to determine predictors of change in health-care service use. All analyses were weighted for sampling and design effects. Additional information was collated and analysed about health system performance from third party surveys and about human resources from the Afghan Ministry of Public Health. Findings Between 2003 and 2015, Afghanistan experienced a 29% decline in mortality of children younger than 5 years. Although definite reductions in maternal mortality remain uncertain, concurrent improvements in essential maternal health interventions suggest parallel survival gains in mothers. In a little over a decade (2003–13 inclusive), coverage of several maternal care interventions increased—eg, for antenatal care (16% to 53%), skilled birth attendance (14% to 46%), and births in a health facility (13% to 39%). Childhood vaccination coverage rates for the basic vaccines from the Expanded Programme of Immunisation (eg, BCG, measles, diphtheria-tetanus-pertussis, and three doses of polio) doubled over this period (about 40% to about 80%). Between 2005 and 2013, the number of deployed facility and community-based health-care professionals also increased, including for nurses (738 to 5766), midwives (211 to 3333), general physicians (403 to 5990), and community health workers (2682 to 28 837). Multivariable analysis of factors contributing to overall changes in skilled birth attendance and facility births suggests independent contributions of maternal literacy, deployment of community midwives, and proximity to a facility. Interpretation Despite conflict and poverty, Afghanistan has made reasonable progress in its reproductive, maternal, newborn, and child health indicators over the last decade based on contributions of factors within and outside the health sector. However, equitable access to health care remains a challenge and present delivery models have high transactional costs, affecting sustainability. To maintain and further accelerate health and development gains, future strategies in Afghanistan will need to focus on investments in improving social determinants of health and targeted cost-effective interventions to address major causes of maternal and newborn mortality. Funding US Fund for UNICEF under the Countdown to 2015 for Maternal, Newborn, and Child Survival grant from the Bill & Melinda Gates Foundation, and from the Government of Canada, Foreign Affairs, Trade and Development Canada. Additional direct and in-kind support was received from the UNICEF Country Office Afghanistan, the Centre for Global Child Health, the Hospital for Sick Children, Toronto, the Aga Khan University, and Mother and Child Care Trust (Pakistan).