BACKGROUND: Impairments in motor control may predicate the paradigm of chronic ankle instability (CAI) that can develop in the year after an acute lateral ankle sprain (LAS) injury. No prospective analysis is currently available identifying the mechanisms by which these impairments develop and contribute to long-term outcome after LAS. PURPOSE: To identify the motor control deficits predicating CAI outcome after a first-time LAS injury. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Eighty-two individuals were recruited after sustaining a first-time LAS injury. Several biomechanical analyses were performed for these individuals, who completed 5 movement tasks at 3 time points: (1) 2 weeks, (2) 6 months, and (3) 12 months after LAS occurrence. A logistic regression analysis of several "salient" biomechanical parameters identified from the movement tasks, in addition to scores from the Cumberland Ankle Instability Tool and the Foot and Ankle Ability Measure (FAAM) recorded at the 2-week and 6-month time points, were used as predictors of 12-month outcome. RESULTS: At the 2-week time point, an inability to complete 2 of the movement tasks (a single-leg drop landing and a drop vertical jump) was predictive of CAI outcome and correctly classified 67.6% of cases (sensitivity, 83%; specificity, 55%; P = .004). At the 6-month time point, several deficits exhibited by the CAI group during 1 of the movement tasks (reach distances and sagittal plane joint positions at the hip, knee and ankle during the posterior reach directions of the Star Excursion Balance Test) and their scores on the activities of daily living subscale of the FAAM were predictive of outcome and correctly classified 84.8% of cases (sensitivity, 75%; specificity, 91%; P < .001). CONCLUSION: An inability to complete jumping and landing tasks within 2 weeks of a first-time LAS and poorer dynamic postural control and lower self-reported function 6 months after a first-time LAS were predictive of eventual CAI outcome.