Joseph was born in March 1743, in the Ohio Country somewhere along the Cuyahoga River. This was during the hunting season when the Mohawk traveled to the area from Kanienkeh ("the Land of the Flint", the Mohawk name for their homeland in what is now upstate New York). He was named Thayendanegea, which in the Mohawk language can mean "two wagers (sticks) bound together for strength", or possibly "he who places two bets." As the Mohawk were a matrilineal culture, he was born into his mother's Wolf Clan. The Haudenosaunee League, of which the Mohawks were one of the Six Nations, was divided into clans headed by clan mothers. Growing up in a society where the chief political figures were the clan mothers gave Brant a respect for women that many Europeans considered odd in the 18th century, but seems very "modern" today. Anglican Church records at Fort Hunter, New York, noted that his parents were Christians and their names were Peter and Margaret Tehonwaghkwangearahkwa. His father died when Joseph was born. One of Brant's friends in later life, John Norton, wrote that Brant's parents were not born Iroquois, but were rather Hurons taken captive by the Iroquois as young people; the Canadian historian James Paxton wrote this claim was "plausible" but "impossible to verify", going on to write that this issue is really meaningless as the Iroquois considered anybody raised as an Iroquois to be Iroquois, drawing no line between those born Iroquois and those adopted by the Iroquois.
After his father's death, his mother Margaret (Owandah), the niece of
Tiaogeara, a Caughnawaga sachem, returned to the province of New York from Ohio with Joseph and his sister Mary (also known as Molly). Molly Brant may actually been Brant's half-sister rather than his sister, but in Mohawk society, they would have been considered full siblings as they shared the same mother. They settled in Canajoharie, a Mohawk village on the Mohawk River, where they had lived before. The Mohawk in common with the other nations of the Haudenosaunee League had a very gendered understanding of social roles with power divided by the male sachrems and chiefs and the clan mothers (who always nominated the male leaders) with decisions reached by consensus between the clan mothers and the chiefs. Mohawk women did all farming (considered woman's work), growing the "Three Sisters" of beans, corn, and squash while men went hunting and engaged in diplomacy and wars. In the society that Brant grew up, there was an expectation that he would be a warrior as a man. .
In the part of the New York frontier where Brant grew up, the area had been settled in the early 18th century by immigrants from the Palatine in what is now Germany known as the Palatines. Relations between the Palatines and Mohawks were friendly with many Mohawk families renting out land to be farmed by the hard-working immigrants (though Mohawk elders complained that their young people were too fond of the beer brewed by the Palatines), and Brant grew up in a multicultural world surrounded by people speaking Mohawk, German and English. Paxton wrote that Brant self-identified as Mohawk, but as someone who grew with the Palatines, Scots and the Irish living in his part of Kanienkeh, the world that he grew up in was not entirely Mohawk, which explains why he was so comfortable with aspects of European culture. The common Mohawk surname Brant was merely the Anglicized version of the common German surname Brandt.
Margaret was a successful businesswomen, who collected and sold ginseng, which was greatly valued for its medical qualities in Europe, selling the plant to New York merchants who shipped it to London. Though her involvement in the ginseng trade, Margaret first met William Johnson, a merchant, fur trader, and land speculator from Ireland, who was much respected by the Mohawk for his honesty, being given the name Warraghiagey ("He Who Does Much Business") and who lived in a mansion known as Fort Johnson by the banks of the Mohawk river. Johnson who was fluent in Mohawk and who lived with two Mohawk women in succession as his common-law wives, had much influence in Kanienkeh. Among the white population, the Butler and Croghan families were close to Johnson while the influential Mohawk families of Hill, Peters and Brant were also his friends. Johnson's Mohawk wife, Caroline, was the niece of the "King Hendrick" who visited London to meet Queen Anne in 1710; Hendrick Peters as the British called the sachem Theyanoguin was not a king, but he was a powerful man in the Mohawk community.
In 1752, Margaret began living with Brant (Canagaraduncka or Kanagradunckwa), a Mohawk sachem, and on March 1753, bore him a son named Jacob, which greatly offended the local Church of England minister, the Reverend John Ogilvie, when he discovered that they were not married. On September 9, 1753 his mother married Kanagradunckwa at the local Anglican church. Kanagradunckwa was also a successful businessman, living in a two-storey European style house with all of the luxuries that would be expected in a middle class English household of the period. Her new husband's family had ties with the British; his grandfather Sagayendwarahton (Old Smoke) was one of the Four Mohawk Kings to visit England in 1710. The marriage bettered Margaret's fortunes, and the family lived in the best house in Canajoharie. Her new alliance conferred little status on her children as Mohawk titles and leadership positions descended through the female line.
Canagaraduncka was a friend of William Johnson, the influential and wealthy British Superintendent for Northern Indian Affairs, who had been knighted for his service. During Johnson's frequent visits to the Mohawk, he always stayed at the Brants' house. Brant's half-sister Molly established a relationship with Johnson, who was a highly successful trader and landowner. His mansion Johnson Hall impressed the young Brant so much that he decided to stay with Molly and Johnson. Johnson took an interest in the youth and supported his English-style education, as well as introducing him to influential leaders in the New York colony. Brant was described as a teenager as an easy-going and affable man who spent his days wandering around the countryside and forests with his circle of friends, hunting and fishing. During his hunting and fishing expeditions, which lasted for days and sometimes weeks, Brant often stopped by at the homes of Palatine and Scots-Irish settlers to ask for food, refreshment and to talk. Brant was well remembered for his charm, with one white woman who led Brant stay with her family for a couple of days in exchange for him sharing some of the deer he killed and to provide a playmate for her boys who were about the same age, recalling after the Revolutionary War that she could never forget his "manly bearing" and "noble goodhearted" ways.
In 1753, relations between the League and the British had become badly strained as land speculators from New York began to seize land belonging to the Iroquois. Led by chief Theyanoguin, known to the British as Hendrick Peters, a delegation arrived in Albany to tell the Governor of New York, George Clinton: "The Covenant Chain is broken between you and us. So brother you are not to expect to hear of me any more and Brother we desire to hear no more of you". The end of the "Covenant Chain" as the Anglo-Iroquois alliance had been known since the 17th century was considered a major change in the balance of power in North America. In 1754, fighting out in the Ohio river valley with the Virginia militia led by George Washington being defeated by the French, and in 1755 a British expedition into the Ohio river valley led by General Edward Braddock was annihilated by the French.
Johnson as superintendent of Indian Affairs, had the task of persuading the Iroquois Six Nations to fight in the Seven Years' War on the side of the British Crown, despite their own inclinations towards neutrality, and on 21 June 1755 called a conference at Fort Johnson with the Iroquois chiefs and clan mothers to ask them to fight in the war, and offered them many presents. As a 12-year-old, Brant attended the conference, though his role was only as an observer who was there to learn the ways of diplomacy. At the Battle of Lake George, Johnson led a force of British Army troops raised in New York together with Iroquois against the French, where he won a costly victory. As the Iroquois disliked taking heavy losses in war owing to their small population, the Battle of Lake George which had cost the Iroquois many dead set off a deep period of mourning across Kanienkeh and much of the Six Nations leadership swung behind a policy of neutrality again. Johnson was to be sorely tried during the next years as the Crown pressed him to get the Iroquois to fight again while most the Six Nations made it clear that they wanted no more fighting. Kanagradunckwa was one of the few Mohawk chiefs who favored continuing to fight in the war, which won him much gratitude from Johnson.