Background: To guide harm-reduction strategies, this study describes alcohol, tobacco, and substance use patterns and injury severity among injury patients presenting to Kilimanjaro Christian Medical Centre (KCMC) in Tanzania. Methods: Self-reported sociodemographic, injury data and Kampala Trauma Score, Alcohol Use Disorder Identification Test (AUDIT), and alcohol, tobacco, and substance use data were collected from a prospective adult trauma registry. Descriptive statistics and multivariable logistic regressions assessed the association of sociodemographic and substance use data with injury severity. Results: Of 716 total participants, 56% self-reported alcohol use within the last year. Of those, 20% had an alcohol use disorder (AUDIT> 8) and 25.6% reported alcohol use prior to injury. 17.1% reported currently using tobacco, and 19.6% reported using a psychoactive substance (marijuana, 2.5% or khat/mirungi, less than 1%). Current alcohol use was associated with high odds of assault. Conclusion: Alcohol use is common among KCMC injury patients. While illicit drug use is rare, it is associated with an increased likelihood of severe injury occurrence. This research highlights the burden of alcohol and substance use related injuries and is necessary to guide both care and policy.