It is the second public university established in the country, as well as the largest university in the Ashanti Region of Ghana.

KNUST has its roots in the plans of Agyeman Prempeh I, a ruler of the Ashanti Kingdom, to establish a university in Kumasi as part of his drive towards modernization of his Ashanti kingdom. This plan never came to fruition due to the clash between British empire expansion and the desire of King Prempeh I to preserve his Ashanti kingdom's independence. However, his younger brother and successor, King Asantehene Agyeman Prempeh II, upon ascending to the Golden Stool in 1935, continued with this vision. Events in the Gold Coast in the 1940s played into his hands. First, there was the establishment of the University College of the Gold Coast. Secondly, there were the 1948 Accra riots and the consequent Watson Commission report, which recommended that a university of sciences be established in Kumasi. Thus, in 1949, the dream of the Prempehs became a reality when building started on what was to be called the Kumasi College of Technology.

The Kumasi College of Technology offered admission to its first students to the engineering faculty in 1951 (however, those students started academic work in 1952), and an Act of Parliament gave the university its legal basis as the Kumasi College of Technology in 1952.^[ The nucleus of the college was formed from 200 teacher training students transferred from Achimota College in the Greater Accra Region. The college was affiliated to the University of London. In 1961, the college was granted full university status.

The university covers a total land area of 2,512.96 acres (1,016.96 ha). The main campus which is about seven square miles in area, is about eight miles (13 km) to the east of Kumasi, the Ashant Regional Capital