In this article, we describe the first, to our knowledge, reported case of severe bacteremic upper urinary tract infection with pyonephrosis-in the context of prior chronic urinary tract disease-caused by community-acquired methicillin-resistant Staphylococcus aureus (MRSA). The patient presented with fever and constitutional symptoms, and computed tomography revealed extensive renal parenchymal infection along with a staghorn calculus and dilatation of the pyelocalyceal system. His clinical condition rapidly deteriorated, and he developed uncontrollable sepsis, necessitating an emergent nephrectomy. Significant pyonephrosis was noted during surgery. Blood cultures yielded MRSA, and molecular analysis (by polymerase chain reaction) of the MRSA strains from blood and wound fluid showed that they were Panton-Valentine leukocidin positive and they also possessed SCCmecA type IV. Postoperatively, the patient was treated with intravenous vancomycin for 3 weeks and had a favorable outcome.