The objective of this case report is to describe the first case of renal actinomycosis caused by Actinomyces meyeri presenting as severe emphysematous pyelonephritis and complicated by septic shock and multi-organ failure. Emphysematous pyelonephritis is a potentially life-threatening infection mostly described in diabetic patients and predominantly caused by uropathogenic bacteria. Actinomycosis is an uncommon chronic infection due to anaerobic gram-positive bacteria that unusually involves the urinary tract. We report the first case of emphysematous pyelonephritis caused by A. meyeri in a 75-year-old non-diabetic woman. The patient presented with an altered status, fever, nausea, and vomiting lasting for 2 days. A computed tomography scan revealed unilateral emphysematous pyelonephritis. She was rapidly admitted to intensive care unit for a septic shock with multiple organ dysfunctions. A conservative management consisting in renal percutaneous drainage, supportive measures, and prolonged adapted antibiotic therapy resulted in complete recovery. This case report illustrates that renal actinomycosis should be considered in case of emphysematous pyelonephritis given the good prognosis of this infection with conservative medical treatment.