Background: Drunk-driving is a major crash risk factor, and crashes resulting from this risky behavior tend to be serious and have significant economic and societal impacts. The presence of passengers and their demographics and activities can influence risky driving behaviors such as drunk-driving. However, passengers could either be an “enabling” factor to take more risks or could be an “inhibiting” factor by ensuring safe driving by a drunk-driver. Objective: This study examines whether the presence of passengers affects the contributing factors of single-vehicle (SV) drunk-driving crashes, by presenting a severity analysis of single- and multi-occupant SV drunk-driving crashes, to identify risk factors that contribute to crash severity outcomes, for the effective implementation of relevant countermeasures. Method: A total of 7407 observations for 2012–2016 from the crash database of the State of Alabama was used for this study. The variables were divided into six classes: temporal, locational, driver, vehicle, roadway, and crash characteristics and injury severities into three: severe, minor, and no injury. Two latent class multinomial logit models—one each for single- and multi-occupant crashes—were developed, to analyze the effects of significant factors on injury severity outcomes using marginal effects. Results: The estimated results show that collision with a ditch, run-off road, intersection, winter season, wet roadway, and interstate decreased the probability of severe injuries in both single- and multi-occupant crashes, whereas rural area, road with downward grade, dark and unlit roadway, unemployed driver, and driver with invalid license increased the likelihood of severe injuries for both single- and multi-occupant crashes. Female drivers were more likely to be severely injured in single-occupant crashes, but less likely in multi-occupant crashes. A significant association was found between severe injuries and weekends, residential areas, and crash location close (<25 mi ≈40.23 km) to the residence of the at-fault driver in multi-occupant crashes. Sport utility vehicles were found to be safer when driving with passengers. Conclusions: The model findings show that, although many correlates are consistent between the single- and multi-occupant SV crashes that are associated with locational, roadway, vehicle, temporal, and driver characteristics, their effect can vary across the single- and multi-occupant driving population. The findings from this study can help in targeting interventions, developing countermeasures, and educating passengers to reduce drunk-driving crashes and consequent injuries. Such integrated efforts combined with engineering and emergency response may contribute in developing a true safe systems approach.