Objectives. To use activity space assessments to investigate neighborhood exposures that may heighten young Black men's vulnerability to substance use and misuse. Methods. We surveyed young Black men in New Haven, Connecticut in 2019 on the locations (activity spaces) they traveled to in a typical week and their experiences of racism and any alcohol and cannabis use at each location. Results. A total of 112 young Black men (mean age = 23.57 years; SD = 3.20) identified 583 activity spaces. There was significant overlap between racism-related events and substance use (alcohol and cannabis use) at specific locations. Areas with a higher prevalence of violent crime also had a greater frequency of racism-related events and substance use. Conclusions. An activity space approach is a promising method for integrating objective and subjective experiences within neighborhood contexts to better understand the frequency and co-occurrence of racism-related stress and substance use among young Black men. (Am J Public Health. 2023;113(S2):S136-S139. https://doi.org/10.2105/AJPH.2023.307254).