This study evaluated the association of self-reported occupational stress and injury among farm and ranch operators in the central United States. Randomly sampled operators received mail surveys with questions related to injuries, chronic health condi-tions, work exposures, and preventive measures in 2018 and 2020. Injury risk factors were analyzed using Poisson regression analysis. Out of 6,744 participants, 836 (12%) reported at least one injury in the past 12 months and 1,766 (26%) reported work-related stress. The percentage of those reporting stress was 24% among those with no injuries, 36% among those with one injury, and 66% among those with two or more injuries. Similar percentages across the three injury categories were found for sleep deprivation (21%, 30%, and 51%) and fatigue (25%, 39%, and 66%). A high perceived stress level was a risk factor for injury in the final adjusted model (adjusted Rate Ratio (aRR): 1.93, 95% CI: 1.65 to 2.25) when controlling for hearing loss (aRR: 1.25, CI: 1.25 to 1.75) and exposure to animal and/or chemical based allergens (aRR: 1.49, CI: 1.17 to 1.91). With musculo-skeletal symptoms (MSS) in the model, the association of stress and injuries was attenuated (aRR: 1.54, CI: 1.32 to 1.79) while MSS had a strong association with injuries (aRR: 3.79, CI: 3.00 to 4.78). Stress, sleep deprivation, and fatigue were associated with injuries in a dose-response manner. Preventing injuries among farmers and ranchers requires a focus on stress reduction and related health conditions.