An active pixel sensor (APS) image sensor comprises an array of pixel circuits corresponding to rows and columns of pixels, a plurality of amplifiers that buffer signals output by the array of pixel circuits, and a plurality of sample and hold circuits that read the buffered signals. A routing mechanism is positioned between the array of pixel circuits and the plurality of amplifiers. A controller selects a set of the pixel circuits for sampling and is configured to control the routing mechanism to couple each pixel circuit in the set to a different one of the amplifiers during a normal mode of operation and to couple each pixel circuit of a subset of pixel circuits in a first set of pixel circuits to a different amplifier of a first subset of the amplifiers, to couple each pixel circuit of a subset of pixel circuits in a second set of pixel circuits to a different amplifier of a second subset of the amplifiers, and to connect the amplifiers of the first and second subsets of amplifiers in pairs to a common one of the sample and hold circuits during a sub-sampling mode of operation.