Recent advances in additive manufacturing (AM) have enabled the fabrication of functionally graded porous biomaterials (FGPBs) for application as orthopedic implants and bone substitutes. Here, we present a step-wise topological design of FGPB based on diamond unit cells to mimic the structure of the femoral diaphysis. The FGPB was manufactured from Ti-6Al-4V powder using the selective laser melting (SLM) technique. The morphological parameters, permeability and mechanical properties of FGPB samples were measured and compared with those of the biomaterials with uniform porous structures based on the same type of the unit cell. The FGPB exhibited a low density (1.9 g/cm3), a moderate Young's modulus (10.44 GPa), a high yield stress (170.6 MPa), a high maximum stress (201 MPa) and favorable ductility, being superior to the biomaterials with uniform porous structures in comprehensive mechanical properties. In addition, digital image correlation (DIC) and finite element (FE) simulation were used to unravel the mechanisms governing the deformation and yielding behavior of these biomaterials particularly at the strut junctions. Both DIC and FE simulations confirmed that the deformation and yielding of the FGPB occurred largely in the load-bearing layers but not at the interfaces between layers. Defect-coupled FE models based on solid elements provided further insights into the mechanical responses of the FGPB to compressive loads at both macro- and micro-scales. With the defect-coupled representative volume element model for the FGPB, the Young's modulus and yield stress of the FGPBs were predicted with less than 2% deviations from the experimental data. The study clearly demonstrated the capabilities of combined experimental and computational methods to resolve the uncertainties of the mechanical behavior of FGPBs, which would open up the possibilities of applying various porosity variation strategies for the design of biomimetic AM porous biomaterials. STATEMENT OF SIGNIFICANCE: Functionally graded bone scaffolds significantly promote the recovery of segmental bone defect. In the present study, we present a step-wise topological design of functionally graded porous biomaterial (FGPB) to mimic the structure of the femoral diaphysis. The Ti-6Al-4V FGPB exhibited a superior combination of low density, moderate Young's modulus, high yield stress and maximum stress as well as favorable ductility. The biomechanical performance of FGPB was studied in both macro and micro perspectives. The defect-coupled model revealed the significant yielding in the load-bearing parts and the Young's modulus and yield stress of the FGPBs were predicted with less than 2% deviations from the experimental data. The superiority of combined experimental and computational methods has been confirmed.