Canassatego only appears in historical documents for the final eight years of his life, and so little is known of his background. His earliest documented appearance is at a treaty conference in Philadelphia in 1742, where he was a spokesman for the Onondaga people, one of the six nations of the Iroquois (Haudenosaunee) League. According to most modern scholars, Canasatego was apparently not one of the fourteen Onondaga hereditary sachems who sat on the Iroquois Grand Council. One modern source disagrees, however, maintaining that Canasatego held the League title of Tadadaho.
In the 1730s, a faction of Iroquois leaders opened a diplomatic relationship with the British Province of Pennsylvania, facilitated by Conrad Weiser, Pennsylvania's interpreter and agent. Pennsylvania agreed to recognize the Iroquois as the owner of all Indian lands in Pennsylvania; the Iroquois, in turn, agreed to sell lands only to Pennsylvania. Canasatego probably attended a 1736 treaty where some Iroquois chiefs sold land along the Susquehanna River to Pennsylvania, even though the Iroquois did not really have a claim to this land.
Canassatego served as the speaker for Onondagas at another conference in 1742, where the Iroquois chiefs collected the final payment for the 1736 land sale. At this meeting, Canassatego managed to convince Governor Thomas Penn to pay more than the original purchase price. Penn, for his part, urged Canassatego to remove the Delaware Indians from the land purchased in the controversial Walking Purchase of 1737. Canassatego complied, berating the Delawares as "women" who had no right to sell land, and ordering them to leave. "You are women; take the Advice of a Wise Man and remove immediately", he told the Delawares. The Iroquois designation of the Delawares as "women" has been the subject of much scholarly writing.
In 1744, Canassatego served as a speaker at the Treaty of Lancaster. Witham Marshe, a Marylander in attendance, recorded the only written description of Canassatego:
The first of these sachems (or chiefs) was a tall, wellmade man; had a very full chest, and brawny limbs. He had a manly countenance, mixed with a good-natured smile. He was about 60 years of age; very active, strong, and had a surprising liveliness in his speech, which I observed in the discourse betwixt him, Mr. Weiser, and some of the sachems.
At the treaty conference were representatives of the Iroquois nations (except the Mohawks), and the provinces of Pennsylvania, Maryland, and Virginia. With King George's War underway, the British colonies needed to cultivate a good relationship with their Iroquois neighbors, who might otherwise become French allies. After a speech by Canassatego, officials from Maryland and Virginia agreed to pay the Iroquois for land in their colonies, even though they knew that the Iroquois had no legitimate claim to those lands. Virginia got the better part of the deal, however: although Canassatego and other Iroquois leaders believed that they had sold only the Shenandoah Valley to Virginia, the official deed gave Virginia much more land than that.
Near the end of the conference, Canassatego gave the colonists some advice:
We have one thing further to say, and that is We heartily recommend Union and a Good Agreement between you our Brethren. Never disagree, but preserve a strict Friendship for one another, and thereby you as well as we will become the Stronger.
Our wise Forefathers established Union and Amity between the Five Nations; this has made us formidable, this has given us great weight and Authority with our Neighboring Nations.
We are a powerful confederacy, and, by your observing the same Methods our wise Forefathers have taken, you will acquire fresh Strength and Power; therefore, whatever befalls you, never fall out with one another.
Canassatego was concerned that the British colonies lacked a coordinated policy to deal with the military threat coming from New France. He made similar recommendations about colonial unity at another conference in 1745. His words became a central part of the Iroquois Influence Thesis, the controversial proposal that the Iroquois League was a model for the United States Constitution.
Canassatego's final appearance at a treaty conference was in August 1749, one year after the end of King George's War. In Philadelphia, he complained that colonists were settling on Native land along the Susquehanna River. He agreed to sell this land to Pennsylvania, but once again, the written document ceded much more land than what had been agreed upon in negotiations.
Canassatego was reportedly assassinated with poison in September 1750. There were several contemporary rumors about why he was killed. Some said that he was killed for taking bribes in exchange for selling lands. Another rumor maintained that he had been poisoned by agents of New France. Historian William Starna argued that Canassatego was probably assassinated by pro-French Iroquois who wanted to repudiate Canassatego's diplomatic ties with Pennsylvania.
After his death, a fictional version of Canasatego appeared in the 1755 novel Lydia: or Filial Piety, by English writer John Shebbeare. Following a literary convention where Native Americans were used to satirize Europeans, Canassatego was portrayed as wise and honest, in stark contrast to the scheming Englishmen he encounters.
USS Canassatego (YN-38/YNT-6/YTM-732), a medium harbor tug of the US Navy, was named for Canasatego.