Motor imagery (MI), the mental rehearsal of a movement without muscle activation, combined with motor practice (MP) improves the performance of athletes and promotes rehabilitation of motor function among patients with brain injury. The actual hand posture influences the mental simulation of hand movements such that the ability of MI to affect corticospinal excitability is enhanced when the actual hand posture is consistent with the imagined movement of the hand. However, how MP combined with matched or mismatched hand posture MI modulates hand motor skill performance and the underlying neural mechanisms remain unclear. Thus, we first investigated whether MI hand posture that was compatible or incompatible with the actual MP influenced motor performance and corticospinal excitability induced by MI combined with MP. Twenty-eight healthy young adults repeatedly imagined either (1) closing their right hand into a fist with the thumb on top of the fingers and then opening the hand before actually performing that exact motor action or (2) performing the same motor skill but first imagining the right thumb touching the little finger before opening the hand . Changes in the peak acceleration of the hand grasp were measured to assess motor performance. The amplitudes of motor-evoked potentials (MEPs) in a target muscle were obtained using transcranial magnetic stimulation to assess corticospinal activation, a measure of primary cortex stimulation, before, immediately after, and 20 min after the performance. When the results of two-way repeated-measures analyses of variance assessing the effects of the protocols and time on the various measurements were found to be significant, post hoc paired t tests with Bonferroni corrections for multiple comparisons were applied. The results showed that both peak grasp acceleration and corticospinal excitability significantly increased immediately and 20 min after task completion (p < 0.05 for all) only when the MI hand posture matched with that of the actual MP. We then determined whether this increased corticospinal activity was associated with decreased short-interval intracortical inhibition, as measured using paired-pulse transcranial magnetic stimulation. Similar to our previous results, we found that short-interval intracortical inhibition was significantly decreased immediately and 20 min after task completion (p < 0.05 for both) only when MI matched MP. We concluded that the increased motor performance and corticospinal excitability induced by MI and MP depended on the match between the hand posture in the MI and MP, and that this increased corticospinal excitability was associated with disinhibition of the primary motor cortex activity.