It rises in the southern Ural Mountains east of the headwaters of the Ural River between Chelyabinsk and Magnitogorsk and flows east with many meanders past Troitsk, Chelyabinsk Oblast to meet the Tobol River near Zverinogolovskoye (formerly the fort of Ust-Uysk). The gold-mining town of Plast (town) is on its headwaters. At the time of the Bashkir War of 1735-40 it was the eastern end of the Orenburg Line of forts and is now approximately part of the border between Russia and Kazakhstan. The Uy is the southernmost river on the east side of the Urals whose waters ultimately reach the Arctic Ocean. South of the Uy waters run to the Ural River which flows south into the Caspian Sea.
The name of the river comes from the Bashkir language, in which it means "valley, lowland".