Pedestrians are vulnerable road users that are directly exposed to road traffic crashes with high odds of resulting in serious injuries and fatalities. Therefore, there is a critical need to identify the risk factors associated with injury severity in pedestrian crashes to promote safe and friendly walking environments for pedestrians. This study investigates the risk factors related to pedestrian, crash, and built environment characteristics that contribute to different injury severity levels in pedestrian crashes in Santiago, Chile from a spatial and statistical perspective. First, a GIS kernel density technique was used to identify spatial clusters with high concentrations of pedestrian crash fatalities and severe injuries. Subsequently, partial proportional odds models were developed using the crash dataset for the whole city and the identified spatial clusters to examine and compare the risk factors that significantly affect pedestrian crash injury severity. The model results reveal higher increases in the fatality probability within the spatial clusters for statistically significant contributing factors related to drunk driving, traffic signage disobedience, and imprudence of the pedestrian. The findings may be utilized in the development and implementation of effective public policies and preventive measures to help improve pedestrian safety in Santiago.