The present study investigates the role of locus of control on chronic pain outcomes and quality of life impacted due to chronic migraine among female migraineurs depending on their smoking status. Two thousand adult US-based females were recruited from a well-known online migraine resource to complete a survey. Participants were required to have a chronic migraine diagnosis (ICD-9/10) to be included in the present study. ANOVA and post hoc tests were conducted to analyze the differences in the outcome across 4 different groups (smokers external locus of control, smoker internal locus of control, non-smoker external locus of control, non-smoker internal locus of control). Results showed that a higher level of external locus of control was related to increased migraine (F (4, 1999) = 173.757, p < 0.001), greater negative life impact due to migraine (F (44, 1999) = 54.224, p < 0.001), and reduced productivity at work (F (67, 1999) = 6.981, p < 0.001) and at home (F (77, 1999) = 9.859, p < 0.001) regardless participants' smoking status, though the smokers in external locus of control (ELC) group had the greatest number of mental health concerns. The current results indicate that the external control belief system negatively impacts physical health as well as quality of life of the female chronic migraineurs regardless of their smoking status. Clinicians treating female migraineurs with a lower internal sense of control over their migraines may report high levels of pain and more difficulties in their lives in general with additional elevated levels of mental health concerns among smokers in this population.