As they traveled the backcountry rivers, her husband, James, concurrently led a group of men by land through the Cumberland Gap.
Donelson made his final journal entry on April 24, 1780, as they arrived at Fort Nashborough. Fort Nashborough, at the time, was a part of North Carolina which later became the site of Nashville, Tennessee.
Conflicts arose almost immediately as the Chicamaugans resented the settlers moving further into their lands. In April 1781, the Chicamaugans, led by Dragging Canoe, visited Fort Nashborough. Charlotte, believing they planned to attack the fort while several of the men were away, left the fort to warn them. As she returned to the fort, she realized the men would not be able to get inside the walls of the fort. Thus, she released the hounds who chased the Chicamaugans, and caused enough confusion that the settlers were able to return safely to the fort.
She died on June 11, 1843 in Nashville. Charlotte and James had 11 children.