In 1816, the West Indian-Guinean Chamber of revenues was merged with the college of commerce to form the General Customs Chamber and College of Commerce. However neither the plantation economy nor trade in other goods flourished as hoped. The traditional trading partners, the coastal Fanti states were subjugated by the Ashantis by 1807. The Danish trading posts were finally abandoned. In 1850, Denmark sold its property and claims on the Gold Coast to Great Britain. The Cape Coast Chamber was later formed out of the Customs Chamber and College of Commerce. In 1894 a deputation from the Cape Coast Chamber of Commerce many of whose members held links to merchants in Great Britain put pressure on the governor to appoint a permanent resident. There was considerable feeling in the colony in support of this move. 

The new Asantehene Agyeman Prempeh I declined this request as well as others, but pressure was building for his kingdom to be brought under British control to prevent the French from doing so. Another travelling commissioner Hendrick Vroom was sent to Kumasi to ask the Asantes to accept a British officer as their friend and advisor. Eventually the Asantes sought to by pass the authority of the British governor by sending an eight person deputation to London to plead for their state's independence, but it was neither recognized nor received. They were simply told to deal directly with the Governor of the then Gold Coast. Three members of the chamber and others were then mandated by the Governor to draft the 1951 constitution. 

The Ghana National Chamber of Commerce and Industry recebtly celebrate the 250th anniversary of the establishment of the first chamber of commerce in the then Gold Coast and 50 years of the enactment of the legal instrument merging all Chambers of commerce in independent Ghana into one Ghana National Chamber of Commerce. 

Prior to independence, there were four separate and independent Chambers of Commerce in Ghana, namely: v The Accra and Eastern province Chamber of Commerce v The Kumasi Chamber of Commerce v The Sekondi/Takoradi Chamber of Commerce v The Ghana Chamber of Commerce 

The first three Chambers mentioned above were composed of expatriate firms and businesses based in the three main trading centers, while the fourth Chamber catered for the indigenous Ghanaian businesses. The first president of Ghana, Osagyefo Dr. Kwame Nkrumah did not fancy the duplicated representation smacking of racial discrimination. He rightly ordered the Chambers to merge. The Ghana National Chamber of Commerce was then established on 8th November, 1961 under an Act of parliament (Executive Instrument No. 196) following the amalgamation of the then existing Chambers of Commerce, which were Nationality based. 

The Executive Instrument was amended by legislative Instrument No.611 of 1968 to streamline some of the internal structures of the Chamber. The Chamber was charged with the following functions: 1. Promotion and protection of trade, commerce, industries and manufacturers in Ghana 2. The collection and circulation of statistics relating to trade, commerce, industry and manufacturers of Ghana. 3. The provision of facilities for the communication and interchange of views between members of the Chamber on one hand and departments of Government, public institution and other associations on the other hand, on matters directly affecting the interests of the Chamber or any member thereof. 4. The printing and publication of newspapers, periodicals, books and other documents for promoting the interest of the Chamber. 5. The establishment and maintenance of libraries and museums for the promotion of trade, commerce, industry and manufacturers of Ghana 6. The promotion and participation in trade fairs in Ghana and elsewhere. 7. To develop linkages with Chambers of Commerce on other parts of the world 8. The promotion of and co-operation with associations or Chamber and other organizations in Ghana discharging similar functions as the Chamber. 9. The grant of donations to local or national charities. 

The chamber has since been an independent, non-political organization dedicated to promoting and protecting the interests of businesses in Ghana. The Ghana Chamber of Commerce and Industry is an association of business operators, firms and industries set up to promote commercial and industrial interests in Ghana.