Background: The incidence of septic arthritis is 2e10/100,000. Morbidity is higher with persistent joint dysfunction in up to 30%. Osteoarthritic knee with infection presents a rare challenge, with no established approach for treatment exists. We present our experience of managing infected degenerative joint disease (DJD) with two-stage primary arthroplasty similar to the management of periprosthetic joint infection. Patients and methods: Four patients presented to us between 2016 and 2018 with advanced DJD associated with coexistent joint sepsis with or without adjacent osteomyelitis. The diagnosis of joint sepsis with periarticular osteomyelitis was made based on clinical presentation, radiographic findings, inflammatory serological markers, and culture of knee joint aspirate. All were operated with primary arthroplasty in two stages of debridement with a static spacer followed by antibiotics and implantation. Discussion: With no established method of treating DJD superadded with infection, our experience adds valuable information in treating the same. Our 2-staged primary arthroplasty had a short antibiotic duration between stages, a mean of 63.5 days, and stopped within 3 days of 2 nd stage reducing hospital stay, morbidity, and cost. Our approach is a very viable method of treating infected DJD with a minimum drug holiday time of two weeks before implantation with a better outcome, reducing the recurrence rate of infection. Though a small number with a minimum follow-up of 24 months, we believe we provide valuable additional information. Conclusion: All patients had painless return to early activities with no signs of recurrent infection. Our approach is a very viable and could serve as a cost-effective method treatment for an infected arthritic knee.