BACKGROUND: Race/ethnicity-related discrimination against Asian Americans increased during the COVID-19 pandemic. Previous studies have found an association between discrimination and use of alcohol and other drugs (AOD) as a form of coping. In this study, we evaluate the association of stress from race/ethnicity-related discrimination and coping with tobacco, alcohol, or cannabis (marijuana or cannabidiol) among Asian Americans during the pandemic. METHODS: We used data from Asian American participants of the Asian American and Native Hawaiian/Pacific Islander (AA & NH/PI) COVID-19 Needs Assessment Project (n = 3,159). We measured COVID-19 discrimination by racial/ethnic discrimination perceived as the greatest stressor, whether racial/ethnic discrimination impacted participants' families, and perceived racial bias. Binary logistic regression examined the association between each AOD outcome, discrimination variables, and other COVID-19 stressors accounting for sociodemographic factors, physical and mental health, and survey medium. RESULTS: Asian Americans used alcohol to cope with COVID-19 pandemic stressors (13.0%) followed by tobacco (4.3%) and cannabis (4.1%). About 24% of Asian Americans reported that racial/ethnic discrimination was the greatest source of stress. Racial/ethnic discrimination was only associated with cannabis use. However, COVID-19 stressors (aside from discrimination) were positively associated with all the AOD outcomes. CONCLUSIONS: Asian Americans' AOD use for stress coping during the pandemic was prevalent. Perceived racial bias was associated with cannabis use, however other pandemic-induced stressors, not discriminatory in nature, were consistently associated with AOD use. Targeted research and policy efforts are warranted to address impacts from diverse stressors while tackling racism and substance use within Asian American communities to facilitate post-pandemic recovery.