Infant mortality rate is a measure of population health and neonatal mortality account for great proportion of these deaths. Underdevelopment might be associated to higher neonatal mortality risk due to assistant related factors. Spatial and temporal distribution of mortality help identifying and developing strategies for interventions. To investigate the cluster areas of asphyxia-associated neonatal mortality and to explore its association with per capita gross domestic product (GDP) in São Paulo State (SP), Brazil. Ecological study including live births residents in SP from 2004-2013. Neonatal deaths (0-27 days) with perinatal asphyxia were defined as intrauterine hypoxia, birth asphyxia or meconium aspiration syndrome written in any line of the Death Certificate. Geoprocessing analytical approach included detection of first order effects through quintiles and spatial moving average maps, followed by second order effects by global and local spatial autocorrelation (Moran and LISA, respectively) before and after smoothing with local Bayesian estimates. Finally, Spearman correlation was applied between asphyxia-associated neonatal mortality and mean per capita GDP rates for the municipalities with significant LISA. There were 6,713 asphyxia-associated neonatal deaths among 5,949,267 live births (rate: 1.13/1000) in SP. Spatial moving average maps showed a non-random distribution among municipalities, with presence of clusters (I = 0.048; p = 0.023). LISA map identified clusters of asphyxia-associated neonatal mortality in the south, southeast and northwest. After applying local Bayes estimates, clusters were more pronounced (I = 0.589; p = 0.001). There was a partial overlap of the areas of higher asphyxia-associated neonatal mortality and lower mean per capita GDP. Spatial analysis identified cluster areas of high asphyxia-associated neonatal mortality and low per capita GDP rates, with a significant negative correlation. This optimized, structured, and hierarchical approach to identify high-risk areas of cause-specific neonatal mortality may be helpful for guiding public health efforts to decrease neonatal mortality.