Joseph Brant was married three times, the first to Christine on 25 July 1765, and had two children, Isaac and Christine.

His wife Christine died probably in the March of 1771 of consumption.

His second wife, Susanna (Christine's half-sister) also died of consumption shortly after the marriage without issue.

In 1780, he married Catherine Adonwentishon Croghan, the daughter of the prominent American colonist, Indian agent, fur trader, and New York-Pennsylvania-Ohio landowner/speculator George Croghan and a Mohawk mother, Catharine Tekarihoga.

They had seven children: Joseph, Jacob, John, Margaret, Catherine Mary and Elizabeth. Through her mother, Catharine Adonwentishon was head of the Turtle clan, the first in rank in the Mohawk Nation. Her birthright was to name the Tekarihoga, the principal sachem of the Mohawk nation.

She named her brother, Henry; through Henry and Catharine, Joseph was able to wield considerable power. After Joseph and Henry's deaths, she then named her youngest son John, who died unmarried. Elizabeth, a daughter of his 3rd marriage, was married to William Johnson Kerr, grandson of Sir William Johnson and Molly Brant, and their child subsequently became Chief. United Empire Loyalists, Thayendanegea's surviving sons, Joseph, Jacob, and John fought in the War of 1812.

Joseph Brant died in his house at the head of Lake Ontario (site of what would become the city of Burlington, Ontario) on November 24, 1807. His last words, spoken to his adopted nephew John Norton, reflect his life-long commitment to his people: "Have pity on the poor Indians. If you have any influence with the great, endeavour to use it for their good." The house was owned by descendants until the late 19th century, and is now the Joseph Brant Museum. In 1850, his remains were carried 34 miles (55 km) in relays on the shoulders of young men of Grand River to a tomb at Her Majesty's Chapel of the Mohawks in Brantford. The City of Brantford and the County of Brant, Ontario, located on part of his land grant, is named for him as is the Erie County, New York Town of Brant. A statue of Brant, located in Victoria Square, Brantford, was dedicated in 1886. The township of Tyendinaga and the Tyendinaga Mohawk Territory Indian reserve are also named for Brant, taking their name from an alternate spelling of his traditional Mohawk name. The neighborhood of Tyandaga in Burlington is also named after Brant, using a simplified spelling of his Mohawk name.

Chief Joseph Brant