Cross-education of strength is the increase in strength of the untrained contralateral limb after unilateral training of the opposite homologous limb. We investigated central and peripheral neural adaptations associated with cross-education of strength. Twenty-three right-handed females were randomized into a unilateral training group or an imagery group. A sub-sample of eight subjects (four training, four imagery) was assessed with functional magnetic resonance imaging (fMRI) for patterns of cortical activation during exercise. Strength training was 6 weeks of maximal isometric ulnar deviation of the right arm, four times per week. Peak torque, muscle thickness (ultrasound), agonist-antagonist electromyography (EMG), and fMRI were assessed before and after training. Strength training was highly effective for increasing strength in trained (45.3%; P < 0.01) and untrained (47.1%; P < 0.01) limbs. The imagery group showed no increase in strength for either arm. Muscle thickness increased only in the trained arm of the training group (8.4%; P < 0.001). After training, there was an enlarged region of activation in contralateral sensorimotor cortex and left temporal lobe during muscle contractions with the untrained left arm (P < 0.001). Training was associated with a significantly greater change in agonist muscle EMG pooled over both limbs, compared to the imagery group (P < 0.05). These results suggest that cross-education of strength may be partly controlled by adaptations within sensorimotor cortex, consistent with previous studies of motor learning. However, this research demonstrates the involvement of temporal lobe regions that subserve semantic memory for movement, which has not been previously studied in this context. We argue that temporal lobe regions might play a significant role in the cross-education of strength.