The first written records of the region come from Arab traders in the 9th and 10th centuries. In medieval times the region was dominated by the Trans-Saharan trade and was ruled by the Mali Empire. In the 16th century the region came to be ruled by the Songhai Empire. The first Europeans to visit the Gambia River were the Portuguese in the 15th century who attempted to settle on the river banks but no settlement of significant size was established. Descendants of the Portuguese settlers remained until the 18th century. In the late 16th century English merchants attempted to begin a trade with the Gambia reporting that it was "a river of secret trade and riches concealed by the Portuguese."

In the early 17th century the French attempted to settle the Gambia but failed. Further English expeditions from 1618 to 1621 including under Richard Jobson were attempted but resulted in huge losses. Merchants of the Commonwealth of England sent expeditions to the Gambia in 1651 but their ships were captured by Prince Rupert the following year. In 1651 the Couronian colonisation of the Gambia had also begun with forts and outposts being erected on several islands. The Courlanders remained dominant until 1659 when their possessions were handed over to the Dutch West India Company. In 1660 the Courlanders resumed possession but the next year were expelled by the newly-formed Royal Adventurers in Africa Company.

In 1667 the rights of the Royal Adventurers to the Gambia were sublet to the Gambia Adventurers but later reverted to the new Royal African Company. 1677 saw the beginning of a century-and-a-half-long struggle between the English and French for supremacy over the Gambia and Senegal. The English possessions were captured several times by the French but in the Treaty of Utrecht in 1713 the British rights to the region were recognised by the French. In the mid-18th century the Royal African Company began having serious financial problems and in 1750 Parliament divested the company of its rights in the region. In 1766 the Crown gained possession of the territory and it formed part of the Senegambia colony. In 1783 Senegambia ceased existing as a British colony.

Following the cessation of Senegambia the colony was in effect abandoned. The only Europeans were traders who existed in a few settlements on the river banks such as Pisania. Following the end of the Napoleonic Wars Alexander Grant was sent to re-establish a presence in the Gambia. He established Bathurst and the British possessions continued to grow in size through a series of treaties. It was administered from Sierra Leone until 1843 when it was given its own Governor but in 1866 merged again with Sierra Leone. The cession of the Gambia to France was proposed in the late 19th century but was met with considerable protest in both the Gambia and in England. In 1888 the colony regained its own government structure and in 1894 the Gambia Colony and Protectorate was properly established along the lines it would continue to hold until independence.