A coupled waveguide–surface plasmon resonance (CWSPR) biosensor based on the Kretschmann configuration is developed. The CWSPR couples the surface plasmon resonance (SPR) mode and the waveguide mode and generates two sharp resonance dips in the reflectivity spectrum. The proposed biosensor not only retains the same sensing sensitivity as that of a conventional SPR device but also yields sharper dips in the reflectivity spectrum and therefore provides an improved measurement precision. The two reflectivity spectrum dips enable the refractive indices and thicknesses of both the self-assembled monolayer and a layer of human serum albumin absorbed dynamically on the sensing surface to be determined directly on a real-time basis. The CWSPR biosensor provides the capability to detect the biomolecular conformational changes that occur in biomolecular kinetic interactions.