In August 2016, Louisiana parishes witnessed record rainfall levels, resulting in catastrophic flooding in the Amite and Comite Rivers. In this study, we analyze the spatial patterns of the social vulnerability index (SVI) in each flood zone within Louisiana parishes of East Baton Rouge, Ascension, and Livingston. We use geographically weighted regression (GWR) models to analyze the relation among spatial distribution of the SVI, flood zones, and impervious surfaces. We found that spatial distribution of population and the SVI varies significantly in the disaster affected area. We also found an increase in impervious/developed areas in all flood zones between 2001 and 2011, which may have augmented flooding intensity. The GWR results indicate that spatial variations in the relationship of the social vulnerability index with flood zones and impervious land cover are significant. The most vulnerable places from a biophysical standpoint did not always overlap with the most vulnerable populations. In conclusion, vulnerability varies over space and is not uniform throughout the disaster affected area. Therefore, timely and accurate estimation of the spatial nature of natural disasters and the specific sub-populations that are differentially affected is required.