The present study described the most recent findings concerning the abundance and distribution of plastic in water, sediment, and fauna in the Nile River of Upper Egypt as an interesting research point. The findings revealed that plastics were abundant in the water, sediments, fish, and crayfish throughout the sites. The Nagaa Hammadi site has the highest abundance of meso- and macroplastics in its water and sediment. African catfish had the highest abundance of meso- and macroplastics compared to the other species, while Nile tilapia had no meso- or macroplastics in its alimentary canal or gills in all sites. The Edfu site has the highest abundance of mesoplastics in the alimentary canals of African catfish, while the Nagaa Hammadi site has the highest abundance of mesoplastics in the gills, and macroplastics appeared only in the alimentary canal of African catfish from the El-wasta site. Only mesoplastics were found in the crayfish’s alimentary canal, with the Nagaa Hammadi site having the highest abundance. No macroplastics were detected in the crayfish’s gills or alimentary canal. Additionally, this work lets us understand how plastics behave in freshwater environments, and it is a step toward decision-makers taking appropriate measures to reduce their risk.