Stigmatization toward people with mental illness is a global problem that has been shown to have negative impact on the quality of life of those affected. In African countries, beliefs in supernatural causes of mental illness is a major driver of societal perceptions towards mental illness. Some healthcare professionals have also been found to share similar perceptions towards patients with mental illness and that the mechanisms of stigma can be redirected towards healthcare professionals, including nurses, who care for people with mental illness. This phenomenon is known as ‘associative stigma.’ Many African immigrant nurses are employed as mental health professionals and are dissatisfied and burned out at work, which may be exacerbated by associative stigma. Little is known about these types of stigma among African immigrant nurses based in the United States. Thus, the purpose of this study was to explore stigma towards individuals with mental illness among U.S.-based African immigrant nurses, the experiences of associative stigma among U.S.-based African immigrant nurses and the association with occupational burnout; and determine whether experiences of associative stigma was related to increased stigmatizing behaviors towards individuals with mental illness. The study was a cross-sectional survey assessing stigma among 73 U.S.-based African immigrant registered nurses and nurse practitioners recruited using voluntary response and snowball sampling methods. The survey utilized the Opening Minds Stigma Scale for Healthcare Providers (OMS-HC) to measure stigma, Clinicians’ Associative Stigma Scale (CASS) for associative stigma, Copenhagen Burnout Inventory (CBI) Scale for occupational burnout, and the modified Bicultural Involvement Questionnaire (M-BIQ) Scale measured the degree of acculturation. Statistical analyses using t-tests, ANOVA, and linear regression were conducted. Over three-fourths of the participants were female (76.7%, n = 56). Over half of the participants had more than ten years of experience as a nurse (54.8%, n = 40). The average age of the participants in the study was 47.19 years (SD = 10.09). The average age at migration of the participants was 26.46 years (SD = 8.73). The average time since migration was 20.42 years (SD = 9.51). The average stigma towards mental illness score was 30.22 points (SD = 7.12), which was a moderate level of stigma (range 15–75). The results of the study suggested that stigma of people with mental illness and occupational burnout have a significant positive association (b = 0.16, p = 0.03). Likewise, associative stigma of African immigrant nurses has a significant positive association with occupational burnout (b = 0.61, p = 0.01). These results implied that stigma toward persons with mental illness and the associative stigma experience of African immigrant nurses who care for them were associated with occupational burnout, and interventions should target these areas in healthcare workplaces to reduce burnout, thereby increasing the quality of care these nurses provide.