The current study investigated whether stressful life events and everyday discrimination experiences were associated with using one or more substances in the past 30‐days and substance use disorder (SUD) among adults experiencing homelessness. We obtained survey data from adults (N = 501) seeking services at a day shelter. Participants self‐reported whether they used cigarettes, other tobacco products, cannabis, alcohol, opioids, amphetamine, and cocaine/crack in the past 30‐days, and the total number of substances used were also calculated. We measured stressful life events and everyday discrimination using validated scales. We used multivariable logistic and negative binomial regression analyses to evaluate hypothesised associations. Results indicated that reporting a higher number of stressful life events was associated with past 30‐days cannabis, tobacco, alcohol, and other substance use, screening positive for a SUD, and using a greater number of substances in the past 30 days. After accounting for stressful life events, everyday discrimination was associated with only past 30‐days cannabis use. Overall, we found that reporting stressful life events was related to current substance use and screening positive for a SUD. Findings suggest that life stressors, and discrimination to a lesser extent, were associated with substance use and SUD among adults experiencing homelessness.