Universal coverage of essential interventions would reduce neonatal deaths by an estimated 71%, benefit women and children after the first month, and reduce stillbirths. However, the packages with the greatest effect (care around birth, care of small and ill newborn babies), have low and inequitable coverage and are the most sensitive markers of health system function. In eight of the 13 countries with the most neonatal deaths (55% worldwide), we undertook a systematic assessment of bottlenecks to essential maternal and newborn health care, involving more than 600 experts. Of 2465 bottlenecks identified, common constraints were found in all high-burden countries, notably regarding the health workforce, financing, and service delivery. However, bottlenecks for specific interventions might differ across similar health systems. For example, the implementation of kangaroo mother care was noted as challenging in the four Asian country workshops, but was regarded as a feasible aspect of preterm care by respondents in the four African countries. If all high-burden countries achieved the neonatal mortality rates of their region’s fastest progressing countries, then the mortality goal of ten per 1000 livebirths by 2035 recommended in this Series and the Every Newborn Action Plan would be exceeded. We therefore examined fast progressing countries to identify strategies to reduce neonatal mortality. We identified several key factors: (1) workforce planning to increase numbers and upgrade specific skills for care at birth and of small and ill newborn babies, task sharing, incentives for rural health workers; (2) financial protection measures, such as expansion of health insurance, conditional cash transfers, and performance-based financing; and (3) dynamic leadership including innovation and community empowerment. Adapting from the 2005 Lancet Series on neonatal survival and drawing on this Every Newborn Series, we propose a country-led, data-driven process to sharpen national health plans, seize opportunities to address the quality gap for care at birth and care of small and ill newborn babies, and systematically scale up care to reach every mother and newborn baby, particularly the poorest.