Purpose: The purpose of this study was to report a case of Clostridium perfringens keratitis, which led rapidly to panophthalmitis, with loss of the eye in a healthy patient. Methods: Clinicopathologic case report, with a brief review of the literature. An otherwise healthy 50-year-old man without known risk factors developed a corneal ulcer, and within 48 hours, he lost all vision, with corneal perforation and panophthalmitis. The eye was enucleated, and the globe was examined histopathologically. Results: The cornea was sampled for Gram staining and cultures, which revealed gram-positive rods and the growth of C. perfringens in the anaerobic culture. The globe revealed corneal necrosis and perforation, with acute inflammation in all layers of the eye. Gram-positive bacilli, consistent with C. perfringens, were identified in the vitreous cavity abscess. Conclusions: C. perfringens endophthalmitis cases from penetrating injuries are fulminant infections, with near universal loss of the eye, whereas C. perfringens keratitis cases are relatively indolent infections. To the best of our knowledge, this is the first report of a C. perfringens keratitis, which led rapidly to panophthalmitis. This aggressive behavior of C. perfringens has not been described previously in human subjects.