Single- and multi-vehicle crashes are a significant issue that has economic and social costs and has therefore gained attention. This study explored the factors associated with injury severity for both single- and multi-vehicle crashes using over 550,000 crash data in Japan from 2019 to 2021. The determinants of road infrastructure and traffic control were identified while considering driver, vehicle, environmental, and accident characteristics, using ordered logit and bias-reduced binomial regression models. Our findings are as follows. Traffic control variables had no significant effect on the injury of single-vehicle crashes. Guardrails were associated with higher severity in both single-vehicle and multi-vehicle crashes at intersections. The impact of the centerline varied between intersections and non-intersections for multi-vehicle crashes. The results of this study provide transportation agencies with important guidance for road infrastructure and transport control.