Importance: Stigma, the prejudice and discrimination attached to mental illness, has been persistent, interfering with help-seeking, recovery, treatment resources, workforce development, and societal productivity in individuals with mental illness. However, studies assessing changes in public perceptions of mental illness have been limited.

Objective: To evaluate the nature, direction, and magnitude of population-based changes in US mental illness stigma over 22 years.

Design, setting, and participants: This survey study used data collected from the US National Stigma Studies, face-to-face interviews conducted as 1996, 2006, and 2018 General Social Survey modules of community-dwelling adults, based on nationally representative, multistage sampling techniques. Individuals aged 18 years or older, including Spanish-speaking respondents, living in noninstitutionalized settings were interviewed in 1996 (n = 1438), 2006 (n = 1520), and 2018 (n = 1171). The present study was conducted from July 2019 to January 2021.

Main outcomes and measures: Respondents reacted to 1 of 3 vignettes (schizophrenia, depression, alcohol dependence) meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria or a control case (daily troubles). Measures included beliefs about underlying causes (attributions), perceptions of likely violence (danger to others), and rejection (desire for social distance).

Results: Of the 4129 individuals interviewed in the surveys, 2255 were women (54.6%); mean (SD) age was 44.6 (16.9) years. In the earlier period (1996-2006), respondents endorsing scientific attributions (eg, genetics) for schizophrenia (11.8%), depression (13.0%), and alcohol dependence (10.9%) increased. In the later period (2006-2018), the desire for social distance decreased for depression in work (18.1%), socializing (16.7%), friendship (9.7%), family marriage (14.3%), and group home (10.4%). Inconsistent, sometimes regressive change was observed, particularly regarding dangerousness for schizophrenia (1996-2018: 15.7% increase, P = .001) and bad character for alcohol dependence (1996-2018: 18.2% increase, P = .001). Subgroup differences, defined by race and ethnicity, sex, and educational level, were few and inconsistent. Change appeared to be consistent with age and generational shifts among 2 birth cohorts (1937-1946 and 1987-2000).

Conclusions and relevance: To date, this survey study found the first evidence of significant decreases in public stigma toward depression. The findings of this study suggest that individuals' age was a conservatizing factor whereas being in the pre-World War II or millennial birth cohorts was a progressive factor. However, stagnant stigma levels for other disorders and increasing public perceptions of likely violence among persons with schizophrenia call for rethinking stigma and retooling reduction strategies to increase service use, improve treatment resources, and advance population health.