Clostridial myonecrosis is a highly fatal infectious disease of the muscle that is caused by pathogenic clostridia. When it occurs in equine muscle, the infection can cause a variety of clinical signs. The present report described a case of acute myonecrosis caused by Clostridium septicum in a horse, which had a favorable clinical evolution. A 6-year-old mare was admitted to a veterinary hospital due to increased volume and lameness in the left pelvic limb after an intramuscular injection of an anti-inflammatory drug. The diagnosis of myonecrosis caused by C. septicum was based on clinical and laboratory findings. The animal showed significant improvement after 5 months of treatment and was discharged from the hospital. There is very limited information regarding myonecrosis caused by C. septicum in horses in Brazil; our study showed that early diagnosis and prompt appropriate treatment can ensure significant improvement and recovery of affected animals.