Motor skill acquisition depends on central nervous plasticity. However, behavioural determinants leading to long lasting corticospinal plasticity and motor expertise remain unexplored. Here we investigate behavioural and electrophysiological effects of individually tailored progressive practice during long-term motor skill training. Two groups of participants practiced a visuomotor task requiring precise control of the right digiti minimi for 6 weeks. One group trained with constant task difficulty, while the other group trained with progressively increasing task difficulty, i.e. continuously adjusted to their individual skill level. Compared to constant practice, progressive practice resulted in a two-fold greater performance at an advanced task level and associated increases in corticospinal excitability. Differences were maintained 8 days later, whereas both groups demonstrated equal retention 14 months later. We demonstrate that progressive practice enhances motor skill learning and promotes corticospinal plasticity. These findings underline the importance of continuously challenging patients and athletes to promote neural plasticity, skilled performance, and recovery.