Poor mental health has become a serious social and public health-care burden. This cross-sectional study used multistage stratified cluster random sampling to gather mental health information from 11,891 adults (18–60 years) employed in various occupations categorized according to the Chinese Standard Occupational Classification. Mental health was measured by the General Health Questionnaire, and participants exceeding the cut-off score were defined as having poor mental health. The overall prevalence of poor mental health was 23.8%. The prevalence of poor mental health was significantly higher in the Han ethnic group than Kazak ethnic group and in health-care workers, teachers, and civil servants compared to manual workers. Females (odds ratios (OR) = 1.139, 95% confidence intervals (CI): 1.012–3.198) and knowledge workers (1.697, 1.097–2.962) were risk factors for poor mental health, while Kazak ethnicity (0.465, 0.466–0.937), other minority status (non-Han) (0.806, 0.205–0.987), and working ≥15 years in the same occupation (0.832, 0.532–0.932) were protective (p < 0.05). We concluded that the general level of mental health in Xinjiang, China, is higher in the Kazak ethnic group than the Han ethnic group. The prevalence of poor mental health is higher among knowledge workers than in manual workers due to high incidences of poor mental health in civil servants, health-care workers, and teachers.