The wake response to three-dimensional forcing of flow over a circular cylinder was studied. Spanwise-segmented dielectric-barrier discharge plasma actuators were mounted on the cylinder in a square wave pattern for active forcing of the cylinder wake. The buried electrodes were placed periodically to create a spanwise-modulated blowing profile, with the aim of targeting three-dimensional instabilities in the wake. Considerable spanwise variation in the wake was achieved, which was a direct consequence of the difference in the location of shed spanwise vortices from the cylinder, along with the generation of streamwise vorticity. Two distinct power levels were used for forcing the flow, with different flow response observed between the two conditions. With low power, the segmented forcing caused the large-scale spanwise structures in the forcing region to lead those in the no-forcing region, with an accompanying shift away from the centerline and generation of streamwise vorticity. While vortex shedding was not substantially attenuated with low-power forcing, the shedding in the near wake was significantly attenuated with high-power forcing. This attenuation in the shedding strength was accompanied by a decrease in the peak shedding frequency, indicating an increase in the formation length. High-power forcing caused elongation of the Kármán vortices due to the induced strain field and strong differential development of the wake shedding frequency. In both forcing regimes, the wake three-dimensionality increased as shown by the increased width of the spectral peaks.