Objectives: To provide a case series and systematic review that explores the clinical manifestations, treatments, and methods for defining tuberculosis diagnoses in patients who have undergone total knee arthroplasty (TKA). Methods: Four patients (three women, one man; average age, 59.5 ± 8.89 years; range, 48-69 years) underwent TKA and were subsequently treated for previously unsuspected knee tuberculosis between January 2013 and December 2019. We also reviewed published cases of tuberculous periprosthetic joint infections (TBPJIs) following TKA through databases of MEDLINE/PubMed, the Cochrane Library, and EMBASE. We reviewed studies that were published between January 1980 and December 2019. Results: In our four cases, the preoperative diagnoses were osteoarthritis (n = 2), rheumatoid arthritis (one case), and Charcot's arthropathy (one case). The main clinical manifestations were knee swelling and pain, without fever, weakness, or weight loss. Comorbidities included multiple joints with rheumatoid arthritis or Charcot's arthropathy, diabetes mellitus, and uremia. One patient had a history of lumbar tuberculosis treated with debridement and intervertebral fusion. Preoperative elevated erythrocyte sedimentation rates (ESRs) were detected in all cases, and elevated C-reactive protein (CRP) levels were observed in three cases. The tuberculosis diagnoses were confirmed via histopathologic analysis (three cases) and second-generation sequencing (one case). Three patients received antituberculosis therapy for 1 year, without surgical intervention. Two-stage exchange arthroplasty was performed in one patient because of prosthesis loosening. Within an average follow-up period of 24.75 months, tuberculosis reactivation was not observed and overall functional improvement was demonstrated. Forty-four TBPJI cases were reported in the literature between January 1980 and December 2019. Most (59.09%) occurred within the first year after the index arthroplasty, and the diagnoses were confirmed by culturing Mycobacterium tuberculosis in 88.64% of cases. Favorable outcomes were achieved in 90.91% of the patients who did not undergo surgery, 71.43% of those treated with debridement, 93.33% undergoing revision arthroplasty, and in 90.91% of those undergoing resection and arthrodesis. Conclusions: Clinical manifestations of knee tuberculosis and TBPJI are atypical. Thus, attention should be paid to finding the causes of increased ESRs and CRP levels, particularly in patients with weakened immune functioning, before performing TKA. Pathological examination is an effective method for diagnosing tuberculosis, although sending multiple specimens for pathological examination is necessary.