An imaging system may include an image sensor array and column randomizing multiplexers. The imaging system may include a data output circuit and image readout circuitry such as analog amplifiers, analog-to-digital converters, and memory circuits. The column randomizing multiplexers may include a first column randomizing multiplexer between the image sensor array and at least some of the image readout circuitry. The first column randomizing multiplexer may randomly connect columns of the image sensor array to the image readout circuitry. The connections made by the first column randomizing multiplexer may be randomized as each row of the image sensor array is read out. The column randomizing multiplexers may include a second column randomizing multiplexer between at least some of the image readout circuitry and the data output circuit. The second column randomizing multiplexer may reorder image data for the image readout circuitry.