To understand mechanisms underlying fine motor control of fingers, it is important to examine not only activation of the motor cortex and spinal cord, but also their connectivity in a comprehensive manner. However, there has been no report demonstrating neural coupling between the two neuroanatomically distant regions. Here we developed a novel noninvasive neuroimaging system, which enabled simultaneous measurement of activitation in the brain and cervical spinal cord as well as assessment of connectivity between them. We investigated BOLD signals during little finger-to-thumb opposition tasks with the right or left hand in 13 right-handed volunteers. We found task-evoked activation in the contralateral primary motor cortex (M1) and also in the C7-T1 segment of the spinal cord. Activity in the C7-T1 segment was consistently higher than that in the C5 segment. Activation was located in the spinal hemicord (SHC) ipsilateral to the moving hand during the right hand movement, although the left hand movement evoked bilateral activations. In a structural equation modeling analysis, we examined effective connectivity across four nodes: right M1, left M1, right C7-T1 SHC, and left C7-T1 SHC. We found a consistently positive influence from the contralateral M1 to the ipsilateral SHC during either hand movement. Additionally, we found larger interhemispheric inhibition from the left to the right M1 during the right hand movement, and a positive influence from the ipsilateral M1 to the contralateral SHC only during the left hand movement. The effective connectivity analysis suggested that the asymmetry of this effective connectivity might explain asymmetry of the spinal cord activation between the right hand and left hand movements. The present study for the first time provided direct evidence of effective connectivity between the motor cortex and spinal cord underlying asymmetry of fine motor control of hands in humans.