Highlights Lower respiratory infections (LRI) are the cause of a significant number of hospitalizations in the US. No previous nationwide study examined geographic variations of LRI mortality rates and their association with underlying factors. There was a shift in the location of LRI hotspots from west coast to southeast over time. Decision tree classifiers could predict LRI mortality hotspots with high accuracies. Higher spring temperature and increased precipitation during winter were among the most substantial predictors of presence or absence of LRI hotspots.