This paper presents a layer-wise stress and deformation analysis of a three-layer beam configuration consisting of two dissimilar orthotropic adherends of different thicknesses that are joined together by a deformable interlayer of finite thickness. Analytical solutions for the case of three-point flexure loading are presented for both compressible and incompressible interlayers. Parametric analysis reveals the influences of asymmetry of moduli and adherend thicknesses, interlayer thickness, and overhang of the beams on the beam compliance. Analytical predictions of beam compliance show very good agreement with finite element results. Experimental measurements of compliance of various unsymmetric beams consisting of aluminum adherends separated by a rubber interlayer were performed in order to validate the analysis. Excellent agreement between measured and predicted compliance values was observed.