BACKGROUND: Experiences of discrimination harm mental and physical health, with the strongest penalty on mental health. Among immigrants, it remains unclear how acculturation-the process by which immigrants acquire the beliefs and practices of a host culture-influences the mental health burden of navigating discrimination. On the one hand, acculturation can be associated with upward social mobility. Conversely, the acculturative process may increase exposure to, and recognition of, discrimination. OBJECTIVES: We examined the relationship between discrimination and mental illness across racial/ethnic groups, and pathways by which acculturation and age relate to the discrimination-mental health relationship. DESIGN: A secondary data analysis using population data from the 2015-2016 California Health Interview Survey. MAIN MEASURES: The Kessler 6-item Psychological Distress Scale (K6) assessed symptoms of psychological distress, with K6 score ≥ 13 associated with severe mental illness. Discrimination was measured using a self-reported measure of lifetime experience of unfair treatment in getting medical care. We used a 5-point acculturation index (constructed by measures of nativity, years living in the USA, and home language use). A weighted logistic regression model predicted mental illness as a function of discrimination. We ran mediational analysis using the Karlson-Holm-Breen method and used predictive margins to present predicted probabilities of mental illness for people reporting discrimination at different acculturation and age levels. KEY RESULTS: There were independent effects on mental illness associated with increased discrimination (OR 3.85, 95% CI = 2.46, 6.03, p < 0.001) and increased acculturation (OR 1.72, 95% CI = 1.24, 2.38, p = 0.001), including when stratified across racial/ethnic groups. Higher levels of acculturation led to a significant increase in discrimination's association with mental illness. There was a higher probability of mental illness in younger age groups than in older age groups. CONCLUSIONS: While discrimination is associated with poor mental health, a stronger link between discrimination and mental illness exists among younger immigrants and immigrants with increased acculturation. Health practitioners should not overlook the mental health needs of younger immigrants and immigrants who may seem more integrated into US society.