He was the son of HBC factor William Sinclair, from Eastaquoy in Harray, and his Cree wife, Nahovway. He was a brother of William Sinclair. James was born in Rupert's Land and educated in Scotland at Edinburgh University.
James Sinclair was appointed by Duncan Finlayson to guide the settler families to Fort Vancouver on the Columbia River. Most of the families were Métis, headed by men who were capable hunters and well-suited to living off the land. They were hired by the Pugets Sound Agricultural Company (PSAC) to settle at company stations in modern Washington state as agriculturalists or pastoralists. In June 1841, the party left Fort Garry with 23 families consisting of 121 people. They followed the Red River north, crossing Lake Winnipeg and traveled in the Saskatchewan River system to Fort Edmonton.
From there they were guided by Maskepetoon, a chief of the Wetaskiwin Cree. Maskepetoon would stay with the party until they reached Fort Vancouver, where he sailed home on board the Beaver. Going through Lake Minnewanka, they eventually reached where the Spray and Bow rivers meet. Following the course of the Spray River valley, the intrepid British colonists then trekked along a tributary, Whiteman's Creek. From here they crossed the Great Divide of the Rocky Mountains, by a new route which became known as Whiteman's Pass.
From the summit, they traveled southwest down the Cross River to its junction with the Kootenay River. They entered the upper Columbia River basin via Sinclair Pass, near present-day Radium Hot Springs. From there they journeyed south-west down to Lake Pend'Oreille, then on to an old fort known as Spokane House, then to Fort Colvile and finally to Fort Vancouver.
When they arrived at Fort Vancouver, they numbered 21 families of 116 people. Fourteen of them were relocated to Fort Nisqually, while the remaining seven families were sent to Fort Cowlitz. Despite such efforts, Britain eventually ceded all claims to land south of the 49th parallel (except the southern tip of Vancouver Island and surrounding Gulf Islands) to the United States by the Oregon Treaty in 1846, as resolution to the Oregon boundary dispute.
Sinclair returned to the Red River Colony. He then traveled to St. Louis, then California and finally back to Oregon Territory. He also traveled to London where he petitioned Parliament on the rights of Métis for a free fur trade, which angered Governor Simpson. He and Governor Simpson eventually overcame their animosity, and Sinclair rejoined the Hudson's Bay Company.
In 1854 Sinclair led a second large group of Red River settlers on a secret journey to Fort Nez Percés. He had been promised 200 head of cattle by the HBC for doing so. Upon reaching the Rockies he followed the Kananaskis River south and made a difficult crossing following the Elk River into the Columbia-Kootenay's. He died in an Indian attack at the Cascades settlement on the Columbia, March 26, 1856.
Mount Sinclair, Sinclair Pass, and Sinclair Canyon in the Canadian Rockies are named for him.