The present study investigated the impact of real-time weather (air temperature, relative humidity, precipitation, wind speed, and solar radiation) on crash injury severity. Recent crash data (January 2016 to April 2021) on Interstate-75 in the state of Kentucky were merged with real-time weather information (retrieved from Kentucky Mesonet stations) at the 1-hour level. The severity index “SI” (i.e., the ratio of percent severe crashes to percent exposure of a specific weather state during the crash period) was introduced to evaluate the impact of different real-time weather states on fatal and severe injury crashes. Furthermore, the standard mixed logit (MXL), correlated mixed logit (CMXL), and correlated mixed logit with heterogeneity in means (CMXLHM) models were fitted and compared to identify the risk factors contributing to crash injury severity while accounting for unobserved heterogeneity. The results showed that the CMXLHM model was statistically superior to the CMXL and MXL models based on various goodness-of-fit measures (e.g., Akaike information criterion “AIC” and McFadden pseudo R-squared). Results from the SI analysis and CMXLHM model showed that real-time weather-related factors (e.g., air temperature ≥ 70 0F and relative humidity ≥ 90 %) were significantly associated with higher severe injury likelihood. Further, driving under the influence (DUI), young drivers, and vehicle travel speed were associated with greater injury severities. On the other hand, presence of horizontal curve, passenger cars, and hourly traffic volume were associated with lower injury severity likelihood. The study outcomes can help in incident management by suggesting specific real-time weather-related states to feed to dynamic message signs (DMS) to enhance travelers’ safety along the interstates.