High density polyethylene (HDPE) is widely used as a bearing material in industrial application because of its low friction and high wear resistance. Reinforcing polymers with the appropriate nanofillers is an effective way to obtain a variety of enhanced material properties. Carbon nanofibers (CNFs) with silane coatings (two thicknesses: 2.8 nm and 46 nm) were added into high density polyethylene (HDPE) to improve the tribological properties of the nanocomposite material. The goal of the present study is to investigate how the mechanical, thermal, and wear behavior of HDPE can be altered by the addition of either pristine or silane treated CNFs at different loading levels (0.5 wt.%, 1 wt.%, and 3 wt.%) and to model the wear of the HDPE/CNF nanocomposites under both dry and lubricated conditions. In this study, the wear and friction tests are performed on a pin-on-disc tribometer under dry, bovine serum, and phosphate buffered saline lubricated conditions. The thermal, mechanical, properties, and biocompatibility of HDPE/CNF nanocomposites are characterized and compared with those of the neat HDPE. The correlations of the wear and factors such as work of fracture, thermal conductivity, and friction force are explored. An energy-based wear model is proposed for the dry sliding condition in which a thermal analysis is derived to trace the friction energy loss in the wear process. A wear model for the lubricated condition is developed with incorporation of elastohydrodynamic lubrication theory and Reye's wear model to predict the long term wear.