ObjectiveTo compare the prevalence of mental health disorders in individuals with facial synkinesis, facial paralysis alone, and the general population.Study DesignRetrospective cohort.SettingEighty‐two health care organizations across the United States.MethodsThe TriNetX Research Network was queried from 2011 to 2021 for patients with facial paralysis without synkinesis, facial paralysis and documented synkinesis, and controls, matched for age, sex, race, and ethnicity. Cases included infectious, iatrogenic, or idiopathic facial paralysis. Patients with pre‐existing depression or anxiety were excluded. Two‐year rates of newly diagnosed depression, anxiety, and mental health prescriptions were compared.ResultsAmong 127,573 patients with facial paralysis, 92.5% (n = 117,976) had facial paralysis alone, and 7.5% (n = 9597) also had documented synkinesis. Compared to controls, patients with facial paralysis alone had increased risks of new depression (8.9% vs 7.3%, P < .001) and anxiety (10.1% vs 9.6%, P < .001), with higher mental health medication rates (16.6% vs 13.1%, P < .001). Patients with documented synkinesis, in comparison to controls, had the highest risks of depression (19.8% vs 8.6%, P < .001), anxiety (20.5% vs 10.5%, P < .001), and prescriptions (28.1% vs 15.8%, P < .001). The 27.8% (n = 2669) of synkinetic patients treated with chemodenervation had lower rates of depression (8.5% vs 23.5%, P < .001), anxiety (9.0% vs 23.8%, P < .001), and prescriptions (21.6% vs 30.0%, P < .001) compared to synkinetic patients who were not.ConclusionFacial paralysis, particularly synkinesis, is linked to increased mental health disorders. Integrating mental health screening and treatment into a comprehensive approach is crucial. Chemodenervation is associated with decreased mental health disorders in synkinesis, highlighting its therapeutic potential.