Frequency-dependent plasticity (FDP) describes adaptation at the synapse in response to stimulation at different frequencies. Its consequence on the structure and function of cortical networks is unknown. We tested whether cortical “resonance,” favorable stimulation frequencies at which the sensory cortices respond maximally, influenced the impact of FDP on perception, functional topography, and connectivity of the primary somatosensory cortex using psychophysics and functional imaging (fMRI). We costimulated two digits on the hand synchronously at, above, or below the resonance frequency of the somatosensory cortex, and tested subjects’ accuracy and speed on tactile localization before and after costimulation. More errors and slower response times followed costimulation at above- or below-resonance, respectively. Response times were faster after at-resonance costimulation. In the fMRI, the cortical representations of the two digits costimulated above-resonance shifted closer, potentially accounting for the poorer performance. Costimulation at-resonance did not shift the digit regions, but increased the functional coupling between them, potentially accounting for the improved response time. To relate these results to synaptic plasticity, we simulated a network of oscillators incorporating Hebbian learning. Two neighboring patches embedded in a cortical sheet, mimicking the two digit regions, were costimulated at different frequencies. Network activation outside the stimulated patches was greatest at above-resonance frequencies, reproducing the spread of digit representations seen with fMRI. Connection strengths within the patches increased following at-resonance costimulation, reproducing the increased fMRI connectivity. We show that FDP extends to the cortical level and is influenced by cortical resonance.