Pixel binning is performed by summing charge from some pixels positioned diagonally in a pixel array. Pixel signals output from pixels positioned diagonally in the pixel array may be combined on the output lines. A signal representing summed charge produces a binned 2×1 cluster. A signal representing combined voltage signals produces a binned 2×1 cluster. A signal representing summed charge and a signal representing combined pixel signals can be combined digitally to produce a binned 2×2 pixel. Orthogonal binning may be performed on other pixels in the pixel array by summing charge on respective common sense regions and then combining the voltage signals that represent the summed charge on respective output lines.