Performance of a unimanual hand motor task results in functional changes in both primary motor cortices (M1(ipsilateral) and M1(contralateral)). The neuronal mechanisms controlling the corticospinal output originated in M1(ipsilateral) and the resting hand during a unimanual task remain unclear. Here, we assessed functional changes within M1(ipsilateral) and in interhemispheric inhibition (IHI) associated with parametric increases in unimanual force. We measured motor-evoked potential (MEP) recruitment curves (RCs) and short-interval intracortical inhibition (SICI) in M1(ipsilateral), IHI from M1(contralateral) to M1(ipsilateral), and the influence of IHI over SICI using transcranial magnetic stimulation at rest and during 10, 30, and 70% of maximal right wrist flexion force. EMG from the left resting flexor carpi radialis (FCR) muscle was comparable across conditions. Left FCR MEP RCs increased, and SICI decreased with increasing right wrist force. Activity-dependent (rest and 10, 30, and 70%) left FCR maximal MEP size correlated with absolute changes in SICI. IHI decreased with increasing force at matched conditioned MEP amplitudes. IHI and SICI were inversely correlated at increasing forces. In the presence of IHI, SICI decreased at rest and 70% force. In summary, we found activity-dependent changes in (1) SICI in M1(ipsilateral), (2) IHI from M1(contralateral) to M1(ipsilateral), and (3) the influence of IHI over SICI in the left resting hand during force generation by the right hand. Our findings indicate that interactions between GABAergic intracortical circuits mediating SICI and interhemispheric glutamatergic projections between M1s contribute to control activity-dependent changes in corticospinal output to a resting hand during force generation by the opposite hand.