After signing the Treaty of Sycamore Shoals (1775), a Cherokee Chief stated, "Brother, we have given you a fine land. But I believe you will have much trouble settling it." This was an astute observation as well as a fateful premonition. Both France and England desired Western territories, including Kentucky, which had caused confusion and conflict for many years. The English only had trading shanties while France established permanent settlements from Canada to New Orleans. Nevertheless, England continually attempted to stake a claim.

On a 1750 Loyal Land Company expedition, Walker crossed Cave Gap, naming the underlying river after the Duke of Cumberland. Walker sought land for settlement, but turned back just short of the Bluegrass Region after climbing a tree and seeing more rough terrain. However, his detailed journal provided valuable insights. 

Later in the same year, the Ohio Land Company hired Christopher Gist for an expedition to the Falls of Ohio. He abandoned the mission 15 miles short of the Falls when warned of hostile French–supporting Native Americans camped there, by their friendly counterparts. Gist returned through the Bluegrass Region, crisscrossing the path of Thomas Walker. 

Concerned with Ohio Valley claims in 1753, Virginia Governor Robert Dinwiddie sent George Washington and advisor Gist on a failed mission to speak with French officials. French–English land disputes continued until France ceded everything east of the Mississippi, except New Orleans, to England in the Treaty of Paris (1763). The Proclamation of 1763 prohibited colonists from settling west of the Appalachians and required any settlers to return east. This allowed England to plan for the region and negotiate with its current occupants — Native Americans.

Native American culture dictated land use that did not necessarily establish possession. The Shawnee and Cherokee claimed and utilized Kentucky lands until Iroquois conquests prevented further use. Subsequently, England negotiated the Treaty of Fort Stanwix (1768) with the Iroquois, for territory east of the Ohio and Tennessee Rivers. However, England negotiated for the same regions with Cherokee tribes. Clashing cultures and overlooked rights culminated in Lord Dunmore’s War.

Reacting to biased treaties, Shawnee Chief Cornstalk led rebellious Native Americans south of the Ohio River, attacking colonists and raiding settlements. In 1773, English soldiers mobilized, and Kentucky settlers, including Daniel Boone, James Harrod, and Isaac Shelby rallied to protect their claims. The forces met at Point Pleasant, in October 1774, and the only battle of Lord Dunmore’s War ensued, with an English victory. The Treaty of Camp Charlotte kept the Shawnee north of the Ohio and protected future river travelers. This was vital for future settlement, but was not the last significant agreement.

During these conflicts, Colonel William Preston, Surveyor of Fincastle County, directed official expeditions for Virginia. Captain Thomas Bullitt headed the 1773 party to survey military grants and demarcate town lots near the Falls of Ohio. The following year, Harrod, a member of Bullitt’s party, founded Harrodstown, the first permanent settlement in Kentucky, and surveyed surrounding areas.

The Proclamation of 1763 forbade private purchases of Native American land, but this prohibition did not stop the Transylvania Company. The Cherokee sold much of western and central Kentucky to Richard Henderson in the Treaty of Sycamore Shoals (1775), negotiated by Boone. Boone then prepared for settlers by blazing what became known as Wilderness Road and founding Boonesborough, intended to be the capital of Henderson’s "Transylvania Colony." The Virginia General Assembly doomed these aspirations by voiding the treaty in 1778.

It took years of exploration, battles, conquest, and negotiation before England securely claimed Kentucky. As predicted, confusion and conflict continued as pioneers established settlements. Controversial land claims, including military grants, Transylvania claims, and squatters led to the Land Act of 1779. Settlers obtaining legal titles often faced contention because surveyors demarcated boundaries by natural landmarks, such as trees and creeks, and existing property lines. The court of land commissioners attempted to sort out overlapping claims, but amateur surveyors and a lack of comprehensive Kentucky maps ensured continuing discord. Nevertheless, settlers yearned for the "Eden of the West," and the region continued to develop.