Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored. We aimed to examine the relationship between OBS and severe headaches or migraines among American adults. This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine via self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation. The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively. The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.