Case:A 43-year-old woman with dermatomyositis presented with Mycobacterium avium complex (MAC) knee septic arthritis with superimposed polymicrobial infection. After poor infection control with antibiotic therapy, she underwent debridement and antibiotic cement spacer placement, followed by knee arthrodesis 6 months later. At 2-year follow-up, she had no pain and was ambulating without assistive devices.Conclusion:As far as we know, this is the first reported case of MAC native-knee septic arthritis successfully treated with antibiotic cement spacer followed by knee arthrodesis. This case sheds insight on treatment strategies for a rare native-knee infection.