The sparse population of Turkmens who live in the Kara-Kum is engaged in sheep and camel herding. Water comes from over 6,000 wells and from the Kara-Kum Canal. The canal was started in 1954, and built in stages; construction work was continuing at the close of the 1990s. The canal is 1375 km/854 mi in length and takes water to Turkmenbashi on the Caspian Sea.

For the first 1100km/684 mi (Kerki to Kazanjik) the canal is open; it is enclosed for the rest of its length. It is allocated 12.9 km³ of water each year from the Amu Darya River, approximately 10% of the total water resources in the Aral Sea Basin; it is the single biggest user of water in the region. The canal provides water to 3,500,000 ha/8,645,000 acres of rangeland, and irrigated approximately 1,000,000 ha/2,470,000 acres of land, most of which is sown with cotton.

Seepage from the canal has resulted in huge lakes and ponds along the canal's length. The rise in groundwater levels has caused salinization of vast tracts of land, so reducing yields; in some cases, land has had to be abandoned. Cotton-growing has been introduced beside the canal in order to afforest parts of the desert, and to restrain the movement of the drifting sands.

The name Kara-Kum is also applied to a smaller desert in Kazakhstan near the Aral Sea.