ImportanceUnderstanding the association between job characteristics and mental health can inform policies and practices to promote employee well-being.ObjectiveTo investigate associations between job characteristics and mental health, work absenteeism, and mental health care use among US adults.Design, Setting, and ParticipantsThis cross-sectional study analyzed data from the 2021 National Health Interview Survey and included adults aged 18 years or older who reported employment during the past 12 months. Data were analyzed from May 2023 to January 2024.ExposuresJob flexibility was assessed as a summative variable to 3 questions: perceived ease of changing one’s work schedule to do things important to oneself or their family, regularity of work schedule changes, and advance notice of work hours. Job security was measured as perceived likelihood of losing one’s job.Main Outcomes and MeasuresMental health outcomes included self-reported serious psychological distress and frequency of anxiety. Work absenteeism was assessed using the number of missed workdays due to illness. Mental health care use was examined for both current and past year use. Multivariable logistic and binomial regression analyses were used to examine associations of interest.ResultsThe analytic sample consisted of 18 144 adults (52.3% [95% CI, 51.5%-53.2%] male; mean age, 42.2 [95% CI, 41.9-42.6] years). Greater job flexibility was associated with decreased odds of serious psychological distress (odds ratio [OR], 0.74 [95% CI, 0.63-0.86]; P < .001) and lower odds of weekly anxiety (OR, 0.89 [95% CI, 0.81-0.97]; P = .008) or daily anxiety (OR, 0.87 [95% CI, 0.79-0.96]; P = .005). Greater job security was associated with decreased odds of serious psychological distress (OR, 0.75 [95% CI, 0.65-0.87]; P < .001) and lower odds of anxiety weekly (OR, 0.79 [95% CI, 0.71-0.88]; P < .001) or daily (OR, 0.73 [95% CI, 0.66-0.81]; P < .001). Greater job flexibility (incidence rate ratio [IRR], 0.84 [95% CI, 0.74-0.96]; P = .008) and job security (IRR, 0.75 [95% CI, 0.65-0.87]; P < .001) were each associated with decreased number of days worked despite feeling ill over the past 3 months. Greater job security was associated with decreased absenteeism in the past year (IRR, 0.89 [95% CI, 0.82-0.98]; P < .014).Conclusions and RelevanceOrganizational policies that enhance job flexibility and security may facilitate a healthier work environment, mitigate work-related stress, and ultimately promote better mental health.