Boone returns from a solo expedition to find Boonesborough eerily empty. A corrupt British officer has kidnapped the settlers, including Boone's family, and forces them into unfriendly Chickesaw tribal lands with the intention of gaining personal control of the territory. He then captures Boone and demands that he sign away all rights to Boonesborough or watch his family and friends be turned over to the tribe. Boone manages to escape, but realizing he has no chance of freeing the captives on his own, he turns to a surprising source of help.
The annual footrace with the Creeks is looming, and everybody in town has big bets on Daniel to win the race against the Creeks' champion, Deerfoot. When Daniel hurts his foot, they fortunately find a good substitute, Jericho Jones, but he is very stubborn, feeling hurt that they never asked him before. Is he capable and willing to win, and pull the town's "fat out of the fire?" And, what are Stinch and Coll up to?
Daniel and Mingo encounter a strangely dressed Indian fighting of a hunting party. After rescuing him they begin to try and unravel who he was and where he came from. Mingo suspects he may be the sole survivor of a tribe wiped out 200 years ago by the Spaniards.
An athletic escaped slave commits a series of brazen, but non-lethal, thefts of furs from trappers in order to secure enough money to buy passage back to Africa. Daniel decides to set a trap and gets more than he bargained for when they cross paths. Upon finally subduing the determined rogue, Daniel finds that his real conflict is with the man the slave has been selling the stolen furs to - a treacherous nemesis he banished years earlier who is back for revenge.
Israel discovers an elderly Indian left to die by his tribe and nurses him back to health. Daniel and Mingo realize that Israel has interfered with a sacred tribal ritual, but when they try to mend the unintentional meddling, they stumble into a hidden conspiracy that may get them killed.
Boone is recruited by a representative of the Governor to capture and return John Benton, a rabble-rousing trouble-seeking ruffian due for an appointment with the hangman's noose. After snaring Benton from the midst of his nefarious companions with a rather unique ploy, Boone drives him on a trek through the wilderness to justice. He finds himself acquiring a grudging respect for the scoundrel along the way. Their path, however, is fraught with danger beyond Benton's wily attempts to escape, including wildlife, Shawnee, Benton's cohorts, and worst of all, treachery ...
Aaron Burr, ex-Vice President, comes to Boonesborough to enlist Daniel to guide him on a long and dangerous journey to the west, but is vague about his reasons for the trek. When Daniel turns him down due to his unease about Burr's secretive intentions, Jericho blindly jumps at the chance to take the offer and earn a hefty fee. After Burr and Jericho leave, Daniel discovers Burr's true mission, and he and Mingo set out to intercept them and save Jericho from his own naivety.
Highlander settlers begin building a settlement on land that belongs to the Cherokee, threatening the peace. Daniel tries to mediate but finds the Highlander's leader is unwilling to negotiate with "savages".
With Daniel and Jericho away and Choctaw chief Gabriel and his warriors on the warpath, a happy and peaceful Thanksgiving is in doubt. Then Rebecca's Irish father Timothy Patrick Bryan shows up and, in order not to disappoint his grandson Israel, who believes his yarns, invites the Indians to Thanksgiving dinner.
Captain Grant shows up at Boonesborough in the middle of the night, looking for Daniel, who is off on a trip with Rebecca. In a big hurry, Grant obtains a horse and starts after them. He catches up to Daniel, but is then immediately shot. He give Dan a letter from the President and directs Dan to take it to New Orleans to deliver it. The two men that shot Grant follow Daniel and Becky all the way, desperate to prevent the delivery of the letter.
Just before Christmas a blizzard drives everyone from their homes to the safety of Boonesborough. Tempers are as short as food when an Indian couple, about to have a baby at any time, show up seeking shelter.
Mingo finds a woman, who claims she is the sole survivor of an Indian massacre, wondering alone in the wilderness. Daniel, Mingo, and a Capt. Ives agree to escort her back to safety but they soon discover she has a hidden agenda.
Daniel and Mingo are taken prisoner by a Spanish officer named de Vaca while on a trip out West. De Vaca mistakes Daniel for someone named Gabriel. After he discovers his error, he forces Daniel to track Gabriel by holding Mingo prisoner.
Daniel and Mingo travel to Florida and meet a traveling magician named Cameron. His illusions impress the Seminole's chief who considers him a god. Cameron then tries to use the same tricks to win over other tribes-hoping to rule them all.
In Salem, Boone is mistaken for one of two army deserters bounty hunter Simon Harman is searching for. Harman intends to return both men to Fort Savage until he learns of Daniel's true identity. He can get much more money for Boone if he turns him over to the British in Quebec.
Col. Barr, recently court-martialed in Virginia, comes to Boonesborough to start over. When Mingo finds an Indian baby with smallpox, which threatens everyone with an epidemic, Barr uses it as an excuse to seize power while Daniel is away.
While Daniel's in Lancaster, Pennsylvania to have a rifle made, an unscrupulous tavern owner tries to obtain his quipu. Given to Daniel by a Shawnee chief, the quipu guarantees him safe passage through Shawnee territory, which the man needs so he can transport, to New Orleans, gold he plans to steal.
As the execution of Edward Eliot is carried out under the supervision of Colonel Calloway, his brother Matthew Eliot, watching from the stockade where he awaits the same fate, vows revenge. After escaping jail, Eliot, and his confederates, kidnaps Jemima and Israel to force Daniel to bring Calloway to him.
In order to stop the British from taking Fort Cumberland, Governor Patrick Henry of Virginia recruits Daniel to lead a small group of men to blow up a bridge at Stover Station. In order to get there in three days they must travel through dangerous Tuscarora territory with the help of Tuscarora Chief Catahecassa.
Cassady was supposed to build a new road in the wilderness around Shawnee land. But when he decides there isn't enough time before winter to build the longer route, he decides to go straight through Shawnee land and into a possible war.
Daniel is taking a boatload of furs to New Orleans when he is jumped and pushed off his boat. When he comes to, he heads to New Orleans to track down the thief. The plot thickens, however, involving a pretty woman, a fight in a hotel lobby, and a search for buried treasure.
William Blunt, an old friend of Boone's, steals a wagon carrying fifty rifles and powder, which he intends to sell to the Shawnee. Daniel, along with Mingo and Jericho, must find Blunt and recover the rifles before a deal with the chief is made.
A group of renegade scalp-hunters led by Rafe Todd robs Boone's cabin and heads upriver. When Daniel finds out, he goes after the men because Mingo and Israel are also upriver retrieving a cache of furs.
Daniel and Mingo find an old man and a small boy while fur trapping. The boy speaks no English and says one word,"Cibola". The old man believes the boy is named for-and knows the location of-the legendary lost city of gold.
It's the year 1775, and Daniel Boone is blazing his Wilderness Road through the Cumberland Gap in the Appalachian Mountains - from North Carolina and Tennessee into Kentucky. With Boone is a wagon train of settlers. On the way, he meets and befriends Mingo.