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Daniel Boone is commissioned by George Washington to build a fort in the territory of Kentucky. The British are talking to the Indian Nations and trying to win them over to their side and it's Washington's hope that Boone and his people will be able to stop their advancement. While scouting the land out Boone helps a Cherokee out who is being hunted by Shawnee...his name is Mingo, an Oxford educated Half-breed, and he and Boone become fast friends. Boone is captured by Dark Panther of the Shawnee and he learns of their plans to attack Boone's fort in Pennsylvania before they can leave and settle in Kentucky.

A dance at Fort Boonesborough is interrupted by Flathead Joseph, a halfbreed slave trader. He has a young Indian girl with him whom he claims is a Cherokee Princess...and a white girl. Her name is Tekawitha McLeod and she is the daughter of the Cherokee Chief Menewa. When Daniel confronts Menewa about this he admits she is white and taken from a raiding party but he wants her back. Daniel refuses when he realizes he knew her family. The Indians are determined to fight to get her back and the settlers of Boonesborough are just as determined to fight to keep her.

Mingo(Ed Ames), wanted DEAD! Daniel Boone(Fess Parker) must capture his friend Mingo and bring him to justice before all Kentucky erupts in war. Daniel's friend Yadkin(Albert Salmi) is a trusted friend to all in Booneborough and among the Cherokee. Yadkin had canoed up river and while meeting with a Cherokee trading party when they were ambushed by a Creek war party. Yadkin was found floating down river by Daniel's son Israel(Darby Hinton). With Cincinnatus(Dal McKennon) removing the slug(bullet) and Rebecca Boone(Patricia Blair) nursing him, he began to pull through. After he recovered enough, Yadkin identified Mingo as the leader of the Creek warriors and as the very man who shot him. To keep Mose(Adam Williams) and the rest of the men of Boonesborough from going out and starting a shooting war with Mingo's tribe, the Cherokee, Daniel sets out promising to bring Mingo back. While Daniel is on Mingo's trail, he is captured by the Cherokee. Daniel is brought before the Cherokee Council of Chiefs led by Chief Matawa(Ford Rainey)...

As Daniel and Yadkin try to find the latest poachers, they meet a Welsh widow with three children who is determined to settle in Shawnee territory in spite of the fact that the tribe has been hostile to settlers in the recent past.

Daniel and Jemima have planned a pleasant father daughter outing in the wilderness, but things take a nightmarish turn when Daniel accidentally cuts himself with an axe and a band of Native Americans kidnaps his daughter.

Lac Duquesne and Daniel Boone were friends once but now Duquesne has turned to river piracy to make his living. When Duquesne steals 5 cases of rifles from a small riverboat on their way to Boonesborough it becomes Daniel's responsibility to get them back before Duquesne can sell them to the Shawnee. Daniel, Mingo and Yadkin set out in pursuit of Duquesne and the rifles.

Major Wellington, a British officer, asks Boone to assist him in the rescue of four British troops who were negotiating a treaty with the Indians. After some hesitation, Daniel Boone agrees to go. Soon, the two men are on a high bluff, looking down at the Wyandot Indian settlement. Wellington pistol whips Boone, and assumes that he has killed him. He removes the buckskin clothes from Boone, puts them on, then throws Daniel Boone into the river below. Wellington enters the Indian camp and presents himself as Daniel Boone. But the scheme falls apart soon thereafter, when the real Daniel Boone walks into the compound. Not knowing who to believe, the Indians set the two men against each in a series of trials to discover the truth.

Simon Girty and his three boys are pelt thieves out to rob Boonesborough of their furs. Daniel, Yadkin and Israel are transporting the furs to Salem to sell them. It's not long before they fall prey to the thieving family and lose their furs, rifles and provisions. Outgunned, Daniel will have to come up with a clever plan to outsmart the Girtys to get their furs back.

After Daniel unwittingly wins the services of two indentured servants for three years, Rebecca moves them into the cabin. Finding this intolerable, Daniel tries to find husbands for the young women.

Daniel runs afoul of Carolina law when he helps Pompey, a runaway slave, remove his leg iron and refuses to turn him over to Calhoun, the bond servant in charge of him.

Russell who has conspired with MacAnders to hide the payroll of massacred British unit arrives from England, kills MacAnders and enlists Daniel to take him and two others to the massacre site while Daniel is visited by MacAnders' ghost.

A British patrol arrives at Boonesborough and announces that all land in the area belongs to the crown colony of Virginia and anyone living there is a trespasser and has 10 days to leave.

Rumors circulate that the British are employing Indians to fight for them. Daniel becomes personally involved when he gets word his wife Rebecca has been taken by an Indian raiding party.

Will Cary, an old acquaintance of Daniel, visits Boonesborough. Dan is pleased to see him, but concerns are raised at Will's activities and where he managed to find so many good trading pelts.

A prophet from the northern tribes arrives in the area asking the local tribes to join in war against the settlers. The tribes refuse until the man offers to kill Daniel Boone as a sign of his power.

A woman accused of witchcraft and her small son flee from a mob and escape to Boonesborough. They are found in the wilderness and nursed back to health by Daniel and Rebecca, but when her husband arrives the hysteria begins again. It is up to Daniel to use courage and wisdom to stand down the charges of witchcraft and help this family of innocent strangers.

A British officer is kidnapped by a group of Shawnee Indians intent on revenge because of his involvement in a massacre. He escapes and Boone finds him and gets involved in reconciling enormous hatred on both sides.

Daniel and Mingo come across the massacre of a Cherokee camp. Mingo is outraged but Boone calms him enough to focus on seeking these men out and bringing them to justice before Cherokee warriors extract their revenge.

Daniel Boone is robbed of his belongings on the trail after seeing the need for rescuing a young boy. Boone escapes and then goes on the hunt for the people that attacked him.

A family of Quakers moves into the area, but refuses to arm themselves against an imminent attack by Cherokees. Their beliefs are sorely tested when the son is attacked and the daughter kidnapped.

Yadkin rounds up and secures the release of four criminals who must now assist Daniel in transporting wagons of weapons from the Carolinas to Kentucky across turf ruled by a merciless criminal gang.

While out hunting, Daniel and Cincinnatus come upon Timothy the peddler just after he has scared off a group of Shawnee. In Boonesborough they learn he's looking for his daughter Becky, Daniel's wife, whom he abandoned when he walked out on her mother many years earlier in Ireland. Their reunion is not a happy one.

Boone and Mingo travel East and get caught up in a confrontation between Benjamin Franklin and British Admiral Lord Clydesdale, who threatens to hang them all for treason.

A bumbling school teacher has come to Boonesborough with the deadly Shawnee hot on his heals. To make matters worse, the town is nearly out of gunpowder.

A French officer named Michelet conspires with the various Indian tribes to lay siege to Boonesborough. The Indians appear to have overwhelming numbers and the cutoff townspeople are desperately short on supplies.

Boone and the people of Boonesborough hole up in the fort using every means possible to fend off the attacking Indians while hoping that a promised British relief force will reach them before it's too late.

A man is found dead by a group of travelers, one of them hears a strange noise and believes it to be the Devil in the form of a black panther. Daniel and Mingo believe a far more mundane explanation is at hand, and investigate to prove their point.

Israel accidentally startles a passing peddler's horse and his goods are ruined. Daniel agrees to compensate him for his loss but matters are complicated when he steals a grieving Indian women's mourning doll.

Jericho and Sumah, the daughter of the Indian chief, want to marry. Daniel proposes a trial engagement. For a month Jericho will live with the Indians and Sumah will live with Boone's family and see if each can adapt to the other culture.