The majority of the world's population lives in urban areas, and regions with the highest under-five mortality rates are urbanising rapidly. This 7-year interrupted time series study measured early access to care and under-five mortality over the course of a proactive community case management (ProCCM) intervention in periurban Mali. Using a cluster-based, population-weighted sampling methodology, we conducted independent cross-sectional household surveys at baseline and at 12, 24, 36, 48, 60, 72 and 84 months later in the intervention area. The ProCCM intervention had five key components: (1) active case detection by community health workers (CHWs), (2) CHW doorstep care, (3) monthly dedicated supervision for CHWs, (4) removal of user fees and (5) primary care infrastructure improvements and staff capacity building. Under-five mortality rate was calculated using a Cox proportional hazard survival regression. We measured the percentage of children initiating effective antimalarial treatment within 24 hours of symptom onset and the percentage of children reported to be febrile within the previous 2 weeks. During the intervention, the rate of early effective antimalarial treatment of children 0-59 months more than doubled, from 14.7% in 2008 to 35.3% in 2015 (OR 3.198, P<0.0001). The prevalence of febrile illness among children under 5 years declined after 7 years of the intervention from 39.7% at baseline to 22.6% in 2015 (OR 0.448, P<0.0001). Communities where ProCCM was implemented have achieved an under-five mortality rate at or below 28/1000 for the past 6 years. In 2015, under-five mortality was 7/1000 (HR 0.039, P<0.0001). Further research is needed to elucidate the mechanisms of action and generalizability of ProCCM.