The river's source is on the western slopes of Mount Loolmalasin and the Ngorongoro Highlands in Arusha Region.

It flows though the southern portion of the Serengeti National Park into Magu Bay[2] of the Speke Gulf of Lake Victoria.

[5] There is considerable farming in the lower reaches of the Simiyu Basin, which causes runoff of fertilizers and pesticides.

[8][9]: 124 There are two rainy seasons, the light one from November into January, and the heavy one from March to May, which result in 700 to 1000 mm of annual rainfall.

[6] Average monthly flow of Simiyu measured at the hydrological station in Magu Mjini Estate, about 10 km above the mouth in m³ / s (1999–2004).