A free-ranging plains garter snake (Thamnophis radix) with a brown, encrusted, cutaneous facial lesion presented depressed, emaciated, and dehydrated. It developed respiratory distress and was later euthanized after it failed to respond to antibiotics and supportive treatment. Disseminated granulomatous disease with prominent lung involvement was diagnosed at necropsy. Intralesional hyaline fungal elements, consisting of septate hyphae, were detected histologically among the necrotic core of granulomas and aggregates of epithelioid macrophages. Ophidiomyces ophiodiicola was cultured from tissue specimens and identification was confirmed using 18S rRNA ITS DNA sequencing. Isolation of O. ophiodiicola from lesions that contain morphologically consistent fungal elements strongly incriminates this fungus as the cause of disease in this garter snake.