Background: People in agriculture face unique stressors and occupational hazards, and relatively little is known about substance use in this population. The purpose of this study was to describe substance use among farmers in Illinois. Methods: We conducted a mail survey of Illinois farmers that included the Brief ASSIST to assess substance use for lifetime and past three-month use of ten different substances. The survey also included questions about farming characteristics, mental health, stress, coping, social support, and demographic characteristics. We used chi-square and non-parametric tests to assess group differences. Results: Alcohol, tobacco, cannabis, and sedatives were most reported as used for a lifetime and in the past three months. About three-quarters of the sample had recently used alcohol. Recent tobacco use was associated with not being married, less education, and less concern about climate-related farm stress. Recent sedative use was associated with greater concern about isolation-related farm stress. People who reported multiple substance use were at a greater risk for suicide and were more likely to meet the criteria for generalized anxiety disorder. None of the participants reported recent use of cocaine, heroin, inhalants, or hallucinogens. Conclusion: Specific social and cultural aspects of farming and farm communities may contribute to substance use among people working in agriculture. Future research can help to better understand this intersection and make recommendations for programs and resources to promote adaptive coping strategies.