Road crashes remain a preventable cause of morbidity and mortality. The rush-hour period represents the time with the highest human and vehicular road densities. This dissertation aims to assess the environmental factors associated with fatal crash injuries during the rush and non-rush hour period, assess the association of substance use and non-fatal crash injuries during the rush and non-rush hour period, and assess the association of crash response time and deaths at crash scenes during the rush and non-rush hour period. To address these aims, nested spatial negative binomial regression, partially proportional ordinal logistic regression, and multivariable logistic regression analyses were performed. During the rush-hour period, the median fatality rate per county was 7.30 per 100,000 population. Highways had the highest fatality risk, after adjusting for the interaction effect of intersection, driveway, ramp, and work-zone. Also, after adjusting for confounders, substance use was associated with over two-fold increased odds of critical and emergent injury outcomes as compared to low acuity injuries. Further, a minute increase in the Emergency Medical Service travel time was associated with increased odds of death-at-the-scene. Crash prevention policies may target the rush hour period to reduce fatal and non-fatal crash injuries.