In a method of operating an image sensor, the image sensor includes a pixel array and a plurality of column driving circuits that are connected to a plurality of columns of the pixel array. A test operation is performed by applying a test pattern to the plurality of column driving circuits while changing a level of a well-bias voltage applied to a transistor included in the plurality of column driving circuits. A bias setting operation for setting the level of the well-bias voltage is performed based on a result of the test operation. An image capture operation for detecting incident light and generating a frame image is performed based on the pixel array, the plurality of column driving circuits and the well-bias voltage set by the bias setting operation.