By means of purposeful material design and melt manipulation, we presented a highly feasible approach to simultaneously improve the mechanical properties, fatigue and wear resistance of the ultrahigh-molecular-weight polyethylene (UHMWPE)-based self-reinforced polyethylene (PE) blend for artificial joint replacement. The fluidity of the PE blend was warranted by blending low-molecular-weight polyethylene (LMWPE) with radiation cross-linked UHMWPE. The use of the cross-linked UHMWPE restrained the molecular diffusion between LMWPE and UHMWPE phases, and hence increased the content of UHMWPE up to 50 wt% under the premise of desirable fluidity for injection molding. Combination of shear flow field and pre-additive precursors successfully induced numerous interlocking shish-kebabs in the LMWPE phase. Mechanical reinforcement was thus attained, where the ultimate tensile strength was significantly improved from 27.6 MPa for the compression-molded UHMWPE to 81.2 MPa for the PE blend, and the impact strength increased from 29.6 to 35.2 kJ m-2. The fatigue and wear resistance were far superior to that of the compression-molded UHMWPE. Compared to the results reported in our previous study (40 wt% UHMWPE), the increased UHMWPE content compelled LMWPE phase melt to flow faster, thus amplifying the shear rate in the interfacial region between two phases and depressing the relaxation of oriented molecular chains. The crystalline orientation was preserved, especially in the inner layer, leading to further enhancement of the mechanical properties. These results suggest such a self-reinforced PE blend is of benefit to lowering the risk of failure and prolonging the life span of the implant under adverse conditions.