Manipulative therapies and exercises are commonly used for the management of chronic ankle instability (CAI), but there is no evidence regarding the efficacy of high-velocity low-amplitude manipulation (HVLA) in addition to ankle therapeutic exercise to improve CAI in adolescent baseball players (ABP). To compare the effects of HVLA plus ankle therapeutic exercise and ankle therapeutic exercise alone on ankle status, pain intensity, pain pressure threshold (PPT), range of motion (ROM) of the ankle joint, and balance ability in ABP with CAI, a single-blinded randomized controlled trial was conducted. A total of 31 ABP with CAI were randomly allocated to the intervention (n = 16) or control (n = 15) groups. The intervention group received HVLA plus resistance exercise twice a week for 4 weeks, while the control group received resistance exercise alone. Ankle status, pain intensity, PPT, ROM, and balance ability were assessed before and after the intervention. The American Orthopedic Foot and Ankle Society scores showed significant group and time interactions (total, p = 0.002; pain, p < 0.001; alignment, p = 0.001). There were significant group and time interactions in pain intensity (resting pain, p = 0.008; movement pain, p < 0.001). For ROM, there were significant group and time interactions on dorsiflexion (p = 0.006) and eversion (p = 0.026). The unipedal stance of the balance ability showed significant group and time interactions in path length (p = 0.006) and velocity (p = 0.006). Adding HVLA to resistance exercises may be synergistically effective in improving the ankle status, pain intensity, ROM, and balance ability in ABP with CAI.