Rotaviruses are the major cause of viral gastroenteritis in infants and young children, producing a significant pediatric disease burden worldwide. The objective of this study was to investigate mutations in the group A human rotaviruses (RoV) in Egypt and their VP6 gene in Egyptian clinical specimens, raw sewage, treated effluents, Nile water, and drinking water samples. A total of 1026 diarrheal specimens were collected from Abo EL-Reesh children hospital between October 2015 and September 2017. Human RoV group A was detected in 22.61% of the clinical specimens. The highest peak of RoV was noticed in autumn and winter. The detection rate of RoV in sewage samples was 88.6% and 65.7% for the influent and effluent samples respectively. Additionally, RoV was detected in 64.29% of river water samples and in 42.86% of drinking water samples. Sequence analysis of the full-length VP6 gene of clinical and environmental samples revealed silent and non-silent mutations compared to RoV Wa reference strain. Different sequences were clearly clustered with genotypes G1P8, G4P6 and G2P4. The low variations between sequences of the VP6 gene in both clinical specimens and environmental samples which contained the same human RoV genotype and also the high similarity between the VP6 genes in samples which contained different human RoV genotypes support the idea of using VP6 as a candidate human RoV recombinant subunit vaccine in Egypt.