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Reducing maternal and neonatal mortality is a critical health priority within Zambia and globally. Although evidence-based clinical interventions can prevent a majority of these deaths, scalable and sustainable delivery of interventions across low-resource settings remains uneven, particularly across rural and marginalized communities. The Zambian Ministry of Health and the Clinton Health Access Initiative implemented an integrated sexual, reproductive, maternal, and newborn health (SRMNH) program in Northern Province aimed at dramatically reducing mortality over four years. Interventions were implemented between 2018 and 2021 across 141 government-owned health facilities covering all 12 districts of Northern Province, the poorest performing province nationwide and home to over 1.4 million people, around six pillars of an integrated health system. Data on institutional delivery and antenatal and postnatal care were collected through the national Health Management Information System (HMIS). A community-based system for capturing birth outcomes was established using existing government tools and community volunteers since HMIS did not include community-based mortality. Baseline and endline population-based mortality rates were compared for program-supported areas. From the earliest period of population-based mortality reporting in 2019 to program end in 2021, there were statistically significant decreases of 41%, 45%, and 43% in maternal, neonatal, and perinatal mortality rates respectively. Between 2017 to 2021, institutional maternal, neonatal, and perinatal mortality rates across entirety of Northern Province reduced by 12%, 40%, and 41%, respectively. Service readiness and coverage for SRMNH services improved dramatically, supporting increased numbers of patients. Significant mortality reductions were achieved over a relatively short period, reinforced through an emphasis on sustainability and strengthening existing government systems. These results were attained through a consciously cost-efficient approach backed by substantially lower levels of external investment relative to prior programs, allowing many of the interventions to be successfully adopted by government within public sector budgets.