Regular physical activity has a positive impact on cognition and brain function. Here we investigated if a single bout of exercise can improve motor memory and motor skill learning. We also explored if the timing of the exercise bout in relation to the timing of practice has any impact on the acquisition and retention of a motor skill. Forty-eight young subjects were randomly allocated into three groups, which practiced a visuomotor accuracy-tracking task either before or after a bout of intense cycling or after rest. Motor skill acquisition was assessed during practice and retention was measured 1 hour, 24 hours and 7 days after practice. Differences among groups in the rate of motor skill acquisition were not significant. In contrast, both exercise groups showed a significantly better retention of the motor skill 24 hours and 7 days after practice. Furthermore, compared to the subjects that exercised before practice, the subjects that exercised after practice showed a better retention of the motor skill 7 days after practice. These findings indicate that one bout of intense exercise performed immediately before or after practicing a motor task is sufficient to improve the long-term retention of a motor skill. The positive effects of acute exercise on motor memory are maximized when exercise is performed immediately after practice, during the early stages of memory consolidation. Thus, the timing of exercise in relation to practice is possibly an important factor regulating the effects of acute exercise on long-term motor memory.