We aimed to investigate the incidence, prevalence, and etiology of sixth cranial nerve (CN6) palsy in the general Korean population. The nationally representative dataset of the Korea National Health Insurance Service–National Sample Cohort from 2006 through 2015 was analyzed. The incidence and prevalence of CN6 palsy were estimated in the cohort population, confirming that incident cases of CN6 palsy involved a preceding disease-free period of ≥4 years. The etiologies of CN6 palsy were presumed using comorbidity conditions. Among the 1,108,256 cohort subjects, CN6 palsy developed in 486 patients during the 10-year follow-up. The overall incidence of CN6 palsy was estimated to be 4.66 per 100,000 person-years (95% confidence interval [CI], 4.26–5.08) in the general population. This incidence increased with age, accelerating after 60 years of age and peaking at 70–74 years of age. The mean male-to-female incidence ratio was estimated as 1.41 in the whole population, and the incidence and prevalence of CN6 palsy showed an increasing trend over time in the study period. Surgical incidence for CN6 palsy was only 0.19 per 100,000 person-years (95% CI, 0.12–0.29). The etiologies were presumed to be vascular (56.6%), idiopathic (27.2%), neoplastic (5.6%), and traumatic (4.9%). In conclusion, the incidence of CN6 palsy increases with age, peaking at around 70 years, and shows a mild male predominance in Koreans.