According to reports, the last comprehensive fish records from the Indus River were published in 1977. Although few recent studies have been conducted, they are limited to some confined localities, and hence there was a gap of comprehensive fish diversity analysis of the Indus River in the Sindh province section. Therefore, the present investigation was performed to describe the fish fauna of the Indus River from its northern to its southern extremities. In order to establish fish diversity and distribution, the study was accomplished from June 2016 to May 2017 covering 8 sampling locations across the river. A total of 44 fish species, belonging to 35 genera, included in 18 families, and 9 orders were recorded. Family Cyprinidae was the most specious with 13 species followed by Bagridae and Cichlidae with 4 species each, and Siluridae with3 species. Alpha Diversity Indices study showed that the ichthyofauna diversity of the River was not high in comparison with previous studies. Shannon's index for the whole Indus River locations was 0.95 and the evenness index was 0.77. Sustained populations of exotic fish species were shown to have established in the Indus River.