This study was aimed at investigating the impact of music on exercise performance and affective response to exercise in individuals with Down syndrome (DS). Twelve individuals with DS completed a treadmill walking protocol in both music and no music conditions. Heart rate (HR), walking steps, rate of perceived exertion (RPE), and enjoyment scores were measured in this study. Participants significantly walked more steps with increased exercise HR and percentage MaxHR achieved under music condition. It is speculated that the involvement of music may motivate participants with DS to exert more effort. However, RPE and enjoyment were not significantly affected by music. The positive effect of music may not be strong enough to interfere with peripheral sensory input since half the participants performed at a vigorous level. Still, the implication of our results showed that music could promote physical performance for health benefits in individuals with DS.