In order to develop preventive measures against lateral ankle sprains, it is essential to have a detailed understanding of the injury mechanism. Under laboratory experimental conditions the examination of the joint load has to be restricted with clear margins of safety. However, in the present case one athlete sprained his ankle while performing a run-and-cut movement during a biomechanical research experiment. 3D kinematics, kinetics, and muscle activity of the lower limb were recorded and compared to 16 previously performed trials. Motion patterns of global pelvis orientation, hip flexion, and knee flexion in the sprain trail deviated from the reference trials already early in the preparatory phase before ground contact. During ground contact, the ankle was rapidly plantar flexed (up to 1240°/s), inverted (up to 1290°/s) and internally rotated (up to 580°/s) reaching its maximum displacement within the first 150 ms after heel strike. Rapid neuromuscular activation bursts of the m. tibialis anterior and the m. peroneus longus started 40–45 ms after ground contact and overshot the activation profile of the reference trials with peak activation at 62 ms and 74 ms respectively. Therefore, it may be suggested that neuromuscular reflexes played an important role in joint control during the critical phase of excessive ankle displacement. The results of this case report clearly indicate that (a) upper leg mechanics, (b) pre-landing adjustments, and (c) neuromuscular contribution have to be considered in the mechanism of lateral ankle sprains.