Chisholm was born in valley of the Lower South River near Antigonish, Nova Scotia, of parents who had migrated there from Inverness-shire, Scotland.

In California, he took part in the evolution of that state's mining laws, but had little success in the goldfields but also practiced medicine, and is credited with rescuing the lives of many miners (his medical skills were later of use during a cholera epidemic in British Columbia).

Possessed of "herculean strength" and standing 6 feet 4 inches (193 cm) tall, and reputedly the strongest man in the Colony, he was appointed a constable during the McGowan's War and in 1860 he was elected by the people of Hope to a convention in New Westminster, the purpose of which was to frame and present an appeal to the Imperial Government to introduce proper government for the Mainland Colony, which was then still ruled near-entirely by Governor James Douglas (a Legislative Assembly for the Colony would not be created until 1864, after Douglas' retirement).

Chisholm was among the first parties to travel to the Big Bend Gold Rush in 1860, nearly losing his life when a snow bridge gave way as he was crossing McCullough Creek and he was swept away, then rescued, unconscious, by a party of miners half a mile downstream.

During this period Chisholm was engaged to lead the partyof Major-General Selby Smyth, militia commander of Canada, and his staff through the mountains from Alberta to Hope.