About 135 BC a loose confederation of five Central Asian nomadic tribes known as the Yüeh-chih wrested Bactria from the Bactrian Greeks. These tribes united under the banner of the Kushan (Kusana), one of the five tribes, and conquered the Afghan area. The zenith of Kushan power was reached in the 2nd century AD under King Kaniska (c. AD 78-144), whose empire stretched from Mathura in north-central India beyond Bactria as far as the frontiers of China in Central Asia.

The Kushans were patrons of the arts and of religion. A major branch of the Silk Road carrying luxury goods and ideas between Rome, India, and China passed through Afghanistan, where a transshipment centre existed at Balkh. Indian pilgrims traveling the Silk Road introduced Buddhism to China during the early centuries AD, and Buddhist Gandhara art flourished during this period. The world's largest Buddha figures (175 feet and 120 feet tall) were carved into a cliff at Bamyan in the central mountains of Afghanistan during the 3rd and 4th centuries AD. Further evidence of the trade and cultural achievement of the period has been recovered at the Kushan summer capital of Bagram, north of Kabul; it includes painted glass from Alexandria; plaster matrices, bronzes, porphyries, and alabasters from Rome; carved ivories from India; and lacquers from China. A massive Kushan city at Delbarjin, north of Balkh, and a major gold hoard of superb artistry near Sheberghan, west of Balkh, also have been excavated.