It rises at on the fringes of the Pamirs in Tajikistan, flowing due west for some 300 km, passing Penjikent before entering Uzbekistan at , where it turns west-to-north-west, flowing past the legendary city of Samarkand, which is entirely dependent on the oasis thus created, until it bends left again to the west north of Navoiy and further to the south-west, passing Bukhara before it loses itself in the desert beyond the city of Karakul (Qorako‘l), not quite reaching the Amu Darya, of which it was formerly a tributary.
The Zeravshan range (or Zeravshan mountains) rises to the south of the river. The range extends over 370 km in the east-west direction along the south of Sughd Province in Tajikistan, reaching the highest point of 5,489 m ( Chimtarga peak) in its central part. South-west of Penjikent the range crosses from Tajikistan into Uzbekistan, where it continues at decreasing elevations (1,500-2,000 m) along the internal border between Samarkand and Surkhandarya provinces, until it blends into the desert south-west of Samarkand.
Zarafshan is also a city in Uzbekistan's Navoiy Province, called "the gold capital of Uzbekistan".