He was an enthusiastic duellist and a shrewd businessman who became a partner in the North West Company and a member of the Beaver Club at Montreal, Lower Canada.

In an account of his exploits, he was described as having "indomitable courage... brave, reckless and domineering, with a decided tendency to seek redress with his own hands," characteristics that made him well-suited to his profession.

[2] According to the 1997 book Lords of the North, by James McDonell and Robert Campbell, the Hotel Macdonald in Edmonton, Alberta was named for him.

MacDonald was small in stature and handicapped since childhood by a withered right arm which led to him being known as Le Bras Croche among his Voyageurs, which prevented him from following the family tradition of a military career.

[3][4] On the advice of his mother's uncle, Major-General Small, MacDonald sailed with Simon McTavish from Scotland to Canada in 1791 to take up employment as a clerk in the North West Company, under the tutelage of Angus Shaw.

Returning to Montreal, he stayed with his sister, Magdalen, and her husband William McGillivray at Chateau St. Antoine, one of the early estates of the Golden Square Mile.

Returning to the north in the spring of 1809, he shared the charge of the Red River Department and possibly helped to establish Fort Gibraltar.

This venture was funded by John Jacob Astor as a subsidiary of the American Fur Company to compete against the NWC in the Oregon Country.

[5] Along with those PFC employees uninterested in working for the NWC, MacDonald led a brigade of about 90 men in ten canoes for Fort William.

Forced to import supplies from Montreal, the Nor'Westers responded by preparing to destroy the Red River Colony established by Lord Selkirk.