Objectives The period of entry into university represents one of vulnerability to substance use for university students. The goal of this study is to document the 12-month prevalence of substance use disorders among first year university students in Kenya, and to test whether there is an association between substance use disorders and mental disorders. Methods This was a cross-sectional online survey conducted in 2019 and 2020 as part of the World Health Organization’s World Mental Health International College Student (WMH-ICS) survey initiative. A total of 334 university students completed the survey. Descriptive statistics were used to summarize the demographic characteristics of the participants. Multivariate logistic regression was used to assess the association between substance use disorder and mental disorders after adjusting for age and gender. Results The 12-month prevalence for alcohol use disorder was 3.3%, while the 12-month prevalence for other substance use disorder was 6.9%. Adjusting for age and gender, there was an association between any substance use disorder and major depression, generalized anxiety disorder, bipolar 1 disorder, intermittent explosive disorder, social anxiety disorder, suicidal ideation, suicide attempt, and non-suicidal self-injury. Conclusion These findings highlight the need to institute policies and interventions in universities in Kenya that address substance use disorders and comorbid mental disorders among first-year students.