A signal processing system and method utilizes a multi-stage amplifier to amplify an input signal. The multi-stage amplifier uses a mixed set of voltage rails to improve the operating efficiency of at least one of the amplification stages while allowing other amplification stages to operate in a predetermined operating mode. Efficiency of at least one of the stages is improved by supplying at least one variable voltage rail to an amplification stage of the multi-stage amplifier. The variable voltage rail varies in response to changes in an input signal voltage to the amplification stage. Accordingly, at least one amplification stage utilizes a variable voltage rail, and all amplification stages are supplied with a set of voltage rails that provides sufficient input signal headroom, thus, providing amplification stage efficiency and adequate voltage to allow operation of all amplification stages.