"Blessed with as many lives as a cat," he recounted his time with the Ojibwa and subsequent explorations in his Travels and Adventures in Canada and the Indian Territories between the years 1760 and 1776 (published New York, 1809), which he dedicated to his friend Sir Joseph Banks. The book is considered an adventure classic and one of the best descriptions of Native Indian life at this time.

In 1761, as they travelled west, Henry was repeatedly warned by the Indians they encountered not to risk his life among the Ojibwe, who remained fiercely loyal to the French. By the time Henry took the warnings seriously, he did not have enough supplies to turn back. He disguised himself as a voyageur and let Campion pass for the proprietor. No one was fooled. When he arrived among the Ojibwe at Michilimackinac, Henry found himself surrounded by sixty of their warriors, "each with his tomahawk in one hand, and scalping knife in the other." The imposingly tall war chief Mihnehwehna/Minweweh coldly reminded him that the English may have conquered the French, but they had not conquered the Ojibwe. On taking New France, the English had neglected to make peace with their Indian allies. Having put to use all of his diplomatic skills for which he would become well known, Henry "inwardly endured the tortures of suspense," before Mineweh declared that he admired Henry's bravery for entering their lands. He said since Henry did not come intending to make war, he could "sleep tranquilly" among them. That winter of 1761–62, a minor Ojibwa chief, Wawatam, adopted Henry as a brother.

Henry's ability to make friends with both the French and their allied Indians greatly facilitated his trading activities. Between 1762 and 1763, Henry did Business at Sault Ste Marie, where he formed friendships with Jean Baptiste Cadotte, Sr. (father of Michel Cadotte) and Sir Robert Davers. However, when they returned to Michilimackinac, Chief Pontiac had already invoked his Indian uprising against British posts in the North West. The Ojibwa warriors famously attacked Fort Michilimackinac. Danvers was killed and Henry, after hiding for a time in the house of Charles Michel de Langlade, was captured by the Ojibwe.

He lived with the Wawatam and his family for nearly a year, following them on their seasonal moves to hunting and fishing territories in lower Michigan. Henry's experiences during this winter of 1763–64, described in his memoirs, are a valuable primary source into Native American life during the fur trade era.

They returned to Michilimackinac in the spring of 1764 to trade their furs, but some of the Ojibwas from Saginaw Bay plotted to kill Henry and Wawatam permitted him to go to Sault Ste Marie to seek the protection of Cadotte. He was still not safe as another Ojibwa chief, Madjeckewiss, followed him there with some of his warriors intent on killing him, and it took Cadotte's diplomatic skills to dissuade them. Soon after this, at last Sir william Johnson held a peace conference at Fort Niagara and both Henry and the Ojibwas attended. Eager to return to Michilimackinac to recover his property, Henry accompanied the expedition of Colonel John Bradstreet from Niagara to Detroit, and from there he went with Captain william Howard's troops who reoccupied Michilimackinac in September, 1764.

In 1765, Henry acquired a license to trade in the Lake Superior region. Combining British capital with French Canadian experience, he formed a partnership with Cadot. For the next few years Henry was able to maintain a complete monopoly over the Lake Superior trade and without competition he was able to charge exorbitant prices. There he also came into contact with the Frontiersman Robert Rogers, though Henry reported that Rogers never paid him for certain services rendered.

Alexander Henry was born at New Brunswick, New Jersey to an educated merchant family related to Matthew Henry. He was the eldest son of John Henry (d. 1766), a merchant whose Father, Alexander Henry (d. 1744), had emigrated to British North America from the West of England to seek his fortune. He received a good education and afterward took an apprenticeship in Business. From the age of twenty, Henry was working as a merchant out of Albany, New York. He made a lucrative but Hazardous living supplying the British army during the French and Indian War (the North American front of the Seven Years' War). In 1760, following Wolfes victory at the Battle of the Plains of Abraham, Henry was placed in charge of three loaded supply bateaux, which followed Lord Amhersts advance along Lake Ontario to Montreal. Henry was the first Englishman known to have visited the area of Milwaukee, in 1760.

In 1767–68 he wintered on the Michipicoten River and entered into a partnership with Sir william Johnson, the Duke of Gloucester and others, forming a company to mine silver found in copper ore on the shores of Lake Superior. The expenses involved made the venture unprofitable and the company wound up its affairs in 1774.

In 1775, Henry took four large and twelve small canoes to explore the territory North West of Lake Superior. Henry, Cadot, Peter Pond, the brothers Thomas and Joseph Frobisher then began to challenge the Hudson's Bay Company. Their group, with forty men, stopped at Cumberland House and afterwards built a trading post on Amisk Lake, the first post to be built north of the Saskatchewan River. In 1776, Henry set off by foot to Fort à la Corne, following the Saskatchewan River, and having satisfied his curiosity secured some furs from the Assiniboines. He then purchased 12,000 additional beaver skins from a trip up the Churchill River from the Chipewyans, and some of his last packs were forcibly acquired from Robert Longmoor, an agent for the Hudson's Bay Company. Laden with furs, Henry returned to Montreal and gave the governor, Sir Guy Carleton, a large map of the western region through which he had travelled.

Henry's imagination was caught by the rich potential of the North West Territories and he sailed to England in the autumn of 1776 with a proposal for the Hudson's Bay Company. Bearing a Letter of introduction from Luc de la Corne to his brother Abbé Joseph-Marie de La Corne de Chaptes, Henry next went to France where he was met with "a most flattering reception". Through the influence of the Abbé, Henry was received by Marie-Antoinette at the French Court. Though a natural raconteur who was used to winning friends with ease, it was a great sadness to Henry for the rest of his days that he was met with nothing other than condescension from the young queen and her court.

Henry returned to British North America in 1777 in partnership with Jean-Baptiste Blondeau, trading at the Michipicoten River and Sault Ste Marie; all the time working closely with his old friend Cadot. Between 1778 and 1781 he visited England three times, developing friendships with Sir Joseph Banks and Daniel Solander. Having discussed the possibility at Banks' residence on Soho Square with him and Solander, on his last trip to England, Henry delivered a detailed plan to Banks for an expedition to find an overland route to the Pacific Ocean. This had seemed possible when they had studied Captain Cook's recent findings, but as it was, Cook had made a mistake so the planned expedition came to nothing.

During the mid-1780s Henry encouraged a friend in New York, william Edgar (1736–1820), to enter the trade in furs with China. Fascinated by the prospects offered by the Pacific coast, Henry passed on his ideas, which he called "my favorite plan," to New York merchant John Jacob Astor. He introduced Astor into the Canadian trade and Astor was Henry's guest during his annual visits to Montreal. In the 1790s, Henry and Astor assisted Simon McTavish and the North West Company in organizing shipments of furs to China. In 1792, a fur trade partnership between John Forsyth, Jacob Jordan and Alexander Ellice attempted to entice Henry and Peter Pond to join them in opposition to the North West Company.

Henry had made a prominent name for himself, and from 1781 he settled in Montreal as a general merchant. He was still very much attached to the fur trade with occasional trips made to Detroit or Michilimackinac, and particularly the latter when he sustained heavy losses following the conclusion of the American Revolution. In 1785, Henry with seventeen of the other most prominent fur traders was a founding member of the Beaver Club at Montreal.

As was the custom with early fur traders, Henry had taken a 'country wife', a Native Indian whose sister was in the same way married to Simon McTavish. By her he was said to have fathered several children, but only one daughter is recorded. In 1785, having by then returned to society at Montreal, he married Julia Calcutt Kittson (1756–1835), "a woman of considerable personal fortitude". She was a native of Limavady and the widow of an Anglo-Irish army officer, John George Kittson (d. 1779), whose home was in Co. Cork but had seen considerable Service in North America. Mrs Julia Henry was the godparent with Sir Isaac Brock of william McGillivray's youngest daughter. It is open to debate whether Julia and Alexander met in Canada, England or Ireland around 1780, but they were the parents of several children, two of whom were born before they were married. Henry was step-father to two Kittsons, and the Father of six known children,

During the 1790s, Henry and another close friend, John Askin, were interested in land speculation in Ohio. One of their ventures, known as the Cuyahoga Purchase, came to naught when the Ohio Indians from whom the land had been acquired at the end of the North West Indian War refused to bring forth their land claims at the Treaty of Greenville. The deeds which had been obtained by Henry and his associates were considered invalid, causing Henry to moan, "We have lost a fortune of at least one million of dollars."

In 1792, Henry and his nephew Alexander Henry the younger together obtained one share in the North West Company for six years. In 1796 he sold his interest to william Hallowell (1771–1838), but continued to buy furs from traders and export them to England. When one of his uninsured shipments was captured by the French in 1801, he suffered a serious financial crisis. In order to repair his fortunes, Henry became a commission merchant and auctioneer in partnership with william Lindsay. Plagued by ill health, he worked hard at a job he did not find satisfying.

In 1809, Henry had written to Askin, "There is only us four old friends (James McGill, Isaac Todd, Joseph Frobisher, and himself) alive, all the new North westards are a parcel of boys and upstarts, who were not born in our time, and supposes they know much more of the Indian trade than any before them." To recapture his exciting past, he wrote a memoir of his life which he published in New York that year and dedicated to his English friend, Sir Joseph Banks. Travels and Adventures in Canada and the Indian Territories, between the years 1760 and 1776 has become a Canadian adventure classic and is still considered as one of the best descriptions of Native Indian life at the time of Henry’s travels.

Despite these reverses of fortune, Henry maintained a secure place in Montreal’s mercantile society. He served as a captain in the militia and from 1794 to 1821 as justice of the peace. He lavishly entertained leading merchants in his home, regularly signed petitions and memorials, and attended parties. He was particularly active in the Beaver Club, reactivated in 1807, of which he was the senior member and on its creation, the vice-chairman. In 1806, he was one of the principal donators to the building of Nelson's Column, Montreal. In 1812, he was appointed vendue master and King's Auctioneer for the district of Montreal, working in partnership with his nephew Norman Bethune, who lived with him at 14 Rue Saint-Urbain. He remained close to his old friends, and Isaac Todd, who Henry enjoyed teasing, returned again to Montreal from his native Ireland to be close to Henry and McGill.