Humans show a tendency to represent pitch in a spatial format. A classical finding supporting this spatial representation is the Spatial-Musical Association of Response Codes (SMARC) effect, reflecting faster responses to low tones when pressing a left/bottom-side key and to high tones when pressing a right/top-side key. Despite available evidence suggesting that the horizontal and vertical SMARC effect may be differently modulated by instrumental expertise and musical timbre, no study has so far directly explored this hypothesis in a unified framework. Here, we investigated this possibility by comparing the performance of professional pianists, professional clarinettists and non-musicians in an implicit timbre judgement task, in both horizontal and vertical response settings. Results showed that instrumental expertise significantly modulates the SMARC effect: whereas in the vertical plane a comparable SMARC effect was observed in all groups, in the horizontal plane the SMARC effect was significantly modulated by the specific instrumental expertise, with pianists showing a stronger pitch-space association compared to clarinettists and non-musicians. Moreover, the influence of pitch along the horizontal dimension was stronger in those pianists who started the instrumental training at a younger age. Results also showed an influence of musical timbre in driving the horizontal, but not the vertical, SMARC effect, with only piano notes inducing a pitch-space association. Taken together, these findings suggest that sensorimotor experience due to instrumental training and musical timbre affect the mental representation of pitch on the horizontal space, whereas the one on the vertical space would be mainly independent from musical practice.