Most of what is known about Kaniska derives from Chinese sources, particularly Buddhist writings. When Kaniska came to the throne is uncertain. His accession has been estimated as occurring between AD 78 and 144; his reign is believed to have lasted 23 years. The year 78 marks the beginning of the Shaka era, a system of dating that Kaniska might have initiated.

Through inheritance and conquest, Kaniska's kingdom covered an area extending from Bukhara (now in Uzbekistan) in the west to Patna in the Ganges Valley in the east, and from the Pamirs (now in Tajikistan) in the north to central India in the south. His capital probably was Purusapura (Peshawar, now in Pakistan). He may have crossed the Pamirs and subjugated the kings of the city-states of Khotan, Kashgar, and Yarkand (now in Chinese Turkistan), who had previously been tributaries of the Han emperors of China. Contact between Kaniska and the Chinese in Central Asia may have inspired the transmission of Indian ideas, particularly Buddhism, to China. Buddhism first appeared in China in the 2nd century AD.

As a patron of Buddhism Kaniska is chiefly noted for having convened the fourth great Buddhist council in Kashmir that marked the beginnings of Mahayana Buddhism. At the council, according to Chinese sources, authorized commentaries on the Buddhist canon were prepared and engraved on copper plates. These texts have survived only in Chinese translations and adaptations. Kaniska was a tolerant king and his coins show that he honoured the Zoroastrian, Greek, and Brahmanic deities as well as the Buddha. During his reign contacts with the Roman Empire led to a significant increase in trade and the exchange of ideas; perhaps the most remarkable example of the fusion of eastern and western influences in his reign was the Gandhara school of art, in which Greco-Roman classical lines are seen in images of the Buddha.