Given substantial regional differences in absolute humidity across the US and our understanding of the relationship between absolute humidity and influenza, we may expect important differences in regional seasonal influenza activity. Here, we assessed cross-seasonal influenza activity by comparing counts of positive influenza A and B rapid test results during the influenza season versus summer baseline periods for the 2016/2017 and 2017/2018 influenza years. Our analysis indicates significant regional patterns in cross-seasonal influenza activity, with relatively fewer influenza cases during the influenza season compared to summertime baseline periods in humid areas of the US, particularly in Florida and Hawaii. The cross-seasonal ratios vary from year-to-year and influenza type, but the geographic patterning of the ratios is relatively consistent. Mixed-effects regression models indicated absolute humidity during the influenza season was the strongest predictor of cross-seasonal influenza activity, suggesting a relationship between absolute humidity and cross-seasonal influenza activity. There was also evidence that absolute humidity during the summer plays a role, as well. This analysis suggests that spatial variation in seasonal absolute humidity levels may generate important regional differences in seasonal influenza activity and dynamics in the US.