Background: Advanced septic arthritis (ASA) is defined as the joint inflammation secondary to bacterial infection with a potentially fatal condition, but with no established approach treatment currently. Two-stage primary total knee arthroplasty (TKA) with an antibiotic-laden cement spacer has been shown to be effective in treating SA of the knee in individual cases. We reported our cases to contribute to current information on two-stage TKA for the treatment of advanced SA in the knee joint Methods: We retrospectively screened the clinical profiles of 11 patients who were suffering from SA in their knee joints and underwent two-stage TKA with an antibiotic-laden cement spacer. Information on inflammatory serological markers was summarised, and statistical comparisons of Hospital for Special Surgery (HSS) scores were performed. The degrees of the range of motion (ROM) in the pre-, interval- and post-operation periods were obtained, and the significance level was set at a p value of <0.05. Results: Infection in the knee joint was eliminated in all 11 patients with the two-stage TKA with an antibiotic-laden cement spacer. C-reactive protein levels returned to normal after 3.4 ± 1.4 weeks (range, 1–6 weeks), whereas erythrocyte sedimentation rate returned to normal levels after 16.3 ± 3.0 weeks (range, 13–23 weeks). The means of HSS scores and ROM degrees significantly increased after the first and second stages of surgery (p < 0.05). Conclusions: Two-stage TKA appears to be an a reliable alternative for the treatment of advanced knee SA, providing an encouraging final clinical outcome in controlling infection, relieving clinical severity and improving the function of the keen joint.