Ultra-high molecular weight polyethylene (UHMWPE)-based conductive nanocomposites with reduced percolation and tunable piezoresistive behavior were prepared via solution mixing followed by compression molding using carbon nanotubes (CNT) and graphene nanoplatelets (GNP). The effect of varying wt% of GNP with fixed CNT content (0.1 wt%) on the mechanical, electrical, thermal and piezoresistive properties of UHMWPE nanocomposites was evaluated. The combination of CNT and GNP enhanced the dispersion in UHMWPE matrix and lowered the probability of CNT aggregation as GNP acted as a spacer to separate the entanglement of CNT with each other. This has allowed the formation of an effective conductive path between GNP and CNT in UHMWPE matrix. The thermal conductivity, degree of crystallinity and degradation temperature of the nanocomposites increased with increasing GNP content. The elastic modulus and yield strength of the nanocomposites were improved by 37% and 33%, respectively, for 0.1/0.3 wt% of CNT/GNP compared to neat UHMWPE. The electrical conductivity was measured using four-probe method, and the lowest electrical percolation threshold was achieved at 0.1/0.1 wt% of CNT/GNP forming a nearly two-dimensional conductive network (critical value, t = 1.20). Such improvements in mechanical and electrical properties are attributed to the synergistic effect of the two-dimensional GNP and one-dimensional CNT which limits aggregation of CNTs enabling a more efficient conductive network at low wt% of fillers. These hybrid nanocomposites exhibited strong piezoresistive response with sensitivity factor of 6.2, 15.93 and 557.44 in the linear elastic, inelastic I and inelastic II regimes, respectively, for 0.1/0.5 wt% of CNT/GNP. This study demonstrates the fabrication method and the self-sensing performance of CNT/GNP/UHMWPE nanocomposites with improved properties useful for orthopedic implants.