Background: A sharp decline in under-5 mortality rates has been observed in Senegal, as in some other parts of Africa, over the last 15 years, associated most obviously with a reduction in malaria transmission that occurred in the same time period. The aim of this study was to analyze variations in under-5 mortality in order to better understand the reasons for the recent decline and the factors associated, and the extent of inequalities. Methods: Demographic surveillance was established in four health districts in central Senegal (Mbour, Bambey, Niakhar and Fatick) in 2008. A population of about 600,000 people in 725 villages served by 54 health posts was monitored until 2010. Data for 128788 children under 5 years of age have been included in the analyses. Random effects Poisson regression was used to assess risk factors for child mortality. Results: The leading causes of death were diarrhoea (26.6%), pneumonia (22.2%), and malaria (10.8%). Children living in more than 5km from a health facility had a 2.2-fold (95%CI 1.9, 2.6) higher risk of mortality than children living nearer to health facilities. Mortality rates were associated with the level of malaria transmission, an increase in the malaria incidence rate in children of 1 per 1,000 per year was associated with a mortality rate ratio of 1.04 (95%CI 1.02, 1.05). Children born to mothers under 16 years of age had a 1.6-fold increased risk of mortality (95%CI 1.1, 2.3) compared to children of older mothers. Conclusions: Under 5 mortality in Senegal decreased by 57% between 1990 and 2015, but national average figures conceal substantial inequalities. Higher rates of mortality are associated with areas of persisting malaria transmission, poverty, and poorer access to health care. Strategies targeting these communities are required to improve child survival and reduce inequalities.