Unimanual motor tasks, specifically movements that are complex or require high forces, activate not only the contralateral primary motor cortex (M1) but evoke also ipsilateral M1 activity. This involvement of ipsilateral M1 is asymmetric, such that the left M1 is more involved in motor control with the left hand than the right M1 in movements with the right hand. This suggests that the left hemisphere is specialized for movement control of either hand, although previous experiments tested mostly right-handed participants. In contrast, research on hemispheric asymmetries of ipsilateral M1 involvement in left-handed participants is relatively scarce. In the present study, left- and right-handed participants performed complex unimanual movements, whereas TMS was used to disrupt the activity of ipsilateral M1 in accordance with a “virtual lesion” approach. For right-handed participants, more disruptions were induced when TMS was applied over the dominant (left) M1. For left-handed participants, two subgroups could be distinguished, such that one group showed more disruptions when TMS was applied over the nondominant (left) M1, whereas the other subgroup showed more disruptions when the dominant (right) M1 was stimulated. This indicates that functional asymmetries of M1 involvement during ipsilateral movements are influenced by both hand dominance as well as left hemisphere specialization. We propose that the functional asymmetries in ipsilateral M1 involvement during unimanual movements are primarily attributable to asymmetries in the higher-order areas, although the contribution of transcallosal pathways and ipsilateral projections cannot be completely ruled out.