Despite advances in orthopedic materials, the development of drug-eluting bone and joint implants that can sustain the delivery of the drug and maintain the necessary mechanical strength in order to withstand loading has remained elusive. Here, we demonstrate that modifying the eccentricity of drug clusters and the percolation threshold in ultrahigh molecular weight polyethylene (UHMWPE) results in maximized drug elution and in the retention of mechanical strength. The optimized UHMWPE eluted antibiotic at a higher concentration for longer than the clinical gold standard antibiotic-eluting bone cement while retaining the mechanical and wear properties of clinically used UHMWPE joint prostheses. Treatment of lapine knees infected with Staphylococcus aureus with the antibiotic-eluting UHMWPE led to complete bacterial eradication and to the absence of detectable systemic effects. We argue that the antibiotic-eluting UHMWPE joint implant is a promising candidate for clinical trials.