Nasser Lake provides more than 95% of the Egyptian freshwater budget. The levels, spatial distributions, and risk assessments of heavy metals and natural radioactivity were investigated in the water and sediments in the main channel and khors (side extensions) of Nasser Lake in January 2017. Several indices were used to determine the quality and pollution degree of the water and sediments. The water indices included the heavy metal pollution index and metal contamination index, while the sediment indices were based on the (a) the metal levels as the enrichment factor and geo-accumulation index, and (b) the radioactivity as radium equivalent activity, absorbed dose rate, and external hazard indices. All index values were lower than their global mean values. Also, the results of the noncarcinogenic human health risk via water ingestion were below the threshold risk level. The obtained results indicate the safely used of Nasser Lake water for different purposes.