Denture base materials need appropriate mechanical and tribological characteristics to endure different stresses inside the mouth. This study investigates the properties of poly(methyl methacrylate) (PMMA) reinforced with different low loading fractions (0, 0.2, 0.4, 0.6, and 0.8 wt.%) of hydroxyapatite (HA) nanoparticles. HA nanoparticles with different loading fractions are homogenously dispersed in the epoxy matrix through mechanical mixing. The resulting density, Compressive Young’s modulus, compressive yield strength, ductility, fracture toughness, and hardness were evaluated experimentally; the friction coefficient and wear were estimated by rubbing the PMMA/HA nanocomposites against stainless steel and PMMA counterparts. A finite element model was built to determine the wear layer thickness and the stress distribution along the nanocomposite surfaces during the friction process. In addition, the wear mechanisms were elucidated via scanning electron microscopy. The results indicate that increasing the concentration of HA nanoparticles increases the stiffness, compressive yield strength, toughness, ductility, and hardness of the PMMA nanocomposite. Moreover, tribological tests show that increasing the nanoparticle weight fraction considerably decreases the friction coefficient and wear loss.