In river Nile and its branches, numerous individuals of red swamp crayfish, Procambarus clarkii, displayed melanised areas in gills. To clarify the cause of these lesions, several isolates of Fusarium spp. were recovered. The fungi were first identified morphologically on culture media. Subsequently, molecular identification was carried out based on the internal transcribed spacer (ITS) region and beta-tubulin gene (TUB2) sequences. Based on GenBank database searches, the causative agent was identified as Fusarium solani. To fulfill Koch`s postulates, an experimental infection was induced using a representative isolate (ESHA-1). The challenged crayfish showed similar lesions noticed on naturally-infected ones, and the pathogen was re-isolated from the lesions of the infected individuals. Zinc oxide nanoparticles (ZnO NPs) exhibited a significant reduction in fungal growth. To our knowledge, this is the first record of Fusarium solani infection in red swamp crayfish inhabiting the River Nile.