This research aimed to evaluate the effects of polycyclic aromatic hydrocarbons (PAHs) on the liver and kidneys of Clarias gariepinus as biomarkers. Specimens of C. gariepinus (18 individuals) were collected from two Delta Nile canals—Bahr Shebeen and El-Bahr El-Pharaounyin Al-Minufiya Governorate, Egypt, during July 2023. A total of 16 PAHs were assessed in the liver of the catfish, and histopathological changes in the liver and kidneys were examined. Results showed that the mean values of 16 PAHs—including naphthalene, acenaphthylene, acenaphthene, phenanthrene, anthracene, fluoranthene, benzo(a)anthracene, chrysene, benzo(b)fluoranthene, benzo(k)fluoranthene, and indeno(1,2,3-cd)pyrene—were higher at site 2 than at site 1. In contrast, the mean values of fluorene and pyrene in the liver were higher at site 1 than at site 2. Additionally, the levels of benzo(a)pyrene, dibenzo(a,h)anthracene, and benzo(g,h,i)perylene were similar at both sites. Histopathological examination revealed that liver samples from site 1 exhibited congested blood vessels and signs of fatty degeneration, with hepatocytes showing patchy necrosis and bile stagnation. The liver of fish from site 2 showed fatty degeneration and hemorrhage of blood vessels. Microscopic observations of the kidneys from fish collected at site 1 indicated necrosis in renal cells, leading to degeneration of the renal corpuscles and vacuolation in the renal tubular cells. In contrast, the kidneys of fish from site 2 exhibited dilated renal tubules with vacuolar degeneration. This study determined that elevated levels of PAHs induced harmful histopathological alterations in the liver and kidneys of catfish. Therefore, technical treatments must be implemented for agricultural, industrial, and sewage waste discharged into the El-Bahr El-Pharaouny Canal.