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David Thompson was born in Westminster, Middlesex, to recent Welsh migrants David and Ann Thompson. When Thompson was two, his father died. Due to the financial hardship with his mother without resources, Thompson and his older brother were placed in the Grey Coat Hospital, a school for the disadvantaged of Westminster. Thompson graduated to the Grey Coat mathematical school, where he was introduced to basic navigation skills.

In 1820, the English geologist, John Jeremiah Bigsby, attended a dinner party given by The Hon. William McGillivray at his home, Chateau St. Antoine, one of the early estates in Montreal's Golden Square Mile. He describes the party and some of the guests in his entertaining book The Shoe and Canoe, giving an excellent description of David Thompson: I was well placed at table between one of the Miss McGillivray's and a singular-looking person of about fifty. He was plainly dressed, quiet, and observant. His figure was short and compact, and his black hair was worn long all round, and cut square, as if by one stroke of the shears, just above the eyebrows. His complexion was of the gardener's ruddy brown, while the expression of his deeply-furrowed features was friendly and intelligent, but his cut-short nose gave him an odd look. His speech betrayed the Welshman, although he left his native hills when very young. I might have been spared this description of Mr David Thompson by saying he greatly resembled Curran the Irish Orator... I afterwards travelled much with him, and have now only to speak of him with great respect, or, I ought to say, with admiration... No living person possesses a tithe of his information respecting the Hudson's Bay countries... Never mind his Bunyan-like face and cropped hair; he has a very powerful mind, and a singular faculty of picture-making. He can create a wilderness and people it with warring savages, or climb the Rocky Mountains with you in a snow-storm, so clearly and palpably, that only shut your eyes and you hear the crack of the rifle, or feel the snow-flakes melt on your cheeks as he talks.

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His complexion was of the gardener's ruddy brown,