Background. Urbanization is a process which alters the structure and function of urban environments. The alteration in the quality of urban environmental conditions has significant implications for health. This applies both to the ecology of insect vectors that may transmit diseases and the burden of disease. Study Objectives. To investigate the relationship between malaria and infectious diarrhea mortality and spatially varied neighborhood environmental quality conditions in a low-income economy. Design. A one time point spatial analysis of cluster-level environmental conditions and mortality data using principal component analysis (PCA), one-way analysis of variance (ANOVA) and generalized linear models (GLMs). Methods. Environmental variables were extracted from the Ghana Census 2000 database while mortality data were obtained from the Ghana Births and Deaths Registry in Accra over the period 1998–2002. Results. Whereas there was a strong evidence of a difference in relative mortality of malaria across urban environmental zones of differing neighborhood environmental conditions, no such evidence of mortality differentials was observed for diarrhea. In addition, whereas bivariate analyses showed a weak to strong evidence of association between the environmental variables and malaria mortality, no evidence of association was found between diarrhea mortality and environmental variables. Conclusion. We conclude that environmental management initiatives intended for infectious disease control might substantially reduce the risk of urban malaria mortality and to a less extent that for urban diarrhea mortality in rapidly urbanizing areas in a low-income setting.