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Cartier had sailed up the magnificent "river of Canada" (as he termed its country) as far as the site of Montreal. By doing so, he opened a main pathway into the continent, a water route that led on to the Great Lakes interior. From there other streams in time gave entry to the wide plains beyond, or ways across to soaring western mountains; from there still other rivers reached through the ranges down to the Pacific. The history of much of Canada to 1800—plus a lot of it thereafter—was to take form along this great St. Lawrence traffic route and its long links to westward. Together they joined the lands from ocean to ocean: first, by fur trade canoe, portage and trail; next by river boat or lake ship; then by rail and highway transport along this Canadian mainstream. Thus, vast regions were finally bound into a transcontinental nation. And in a real sense, it all went back to Cartier's opening of the strategic St. Lawrence gate.

In his own day, Cartier's voyages led chiefly to an unsuccessful French attempt to plant a colony at Quebec on the mid-St. Lawrence in 1541–43. Colonized or not, however, the great valley entry attracted ships and commerce; over the next half-century, fishing, whaling and fur trading reached up the lower river. And so, not long after the founding of Port Royal, the French company behind it resolved to shift its centre of operations to the larger opportunities of the St. Lawrence. In 1608 it set a new post at Quebec, where narrows backed by crowning heights commanded the flow of traffic down river. The move succeeded, in the capable hands of Samuel de Champlain, the company's lieutenant "in the country of New France." He had only a handful of men in the little walled and moated wooden habitation that was built below the steeps of Cape Diamond. Yet he added an inland fur empire to the French St. Lawrence domain.

Journeying upstream by canoe, Champlain made contact with fur supplying tribes of the interior, reaching Lake Huron from the Ottawa in 1615 and crossing south to Lake Ontario. In the process, he forged an economic partnership between Indians and Europeans that proved essential to the fur trade. By this means Quebec's trading hinterland was extended to the heart of the Great Lake region, where the Huron people, village-dwelling corn farmers, settled between Lakes Huron and Ontario, served as middlemen in the French fur trade, transmitting trade goods to neighbouring tribes for pelts that were forwarded to the St. Lawrence. Quebec thrived as the base of this wide fur enterprise, but it was still a company commercial depot, scarcely yet a colony. At Champlain's death in 1635 there were less than 200 inhabitants in the tiny capital of a wilderness New France. Nevertheless, some farming had belatedly begun; Trois-Rivieres had been founded as an advanced post upriver; while in 1642 Montreal was established as a still more distant and exposed mission-fort, which was destined to become the main headquarters of the inland fur trade.

At the same time, French Jesuit missionaries were devotedly at work in the villages of the Huron country. There in 1639 they built their mission-centre, Ste. Marie, beside Georgian Bay, with stone bastions, a chapel and hospital, the first European construction in the interior. But very soon violent war erupted between the Hurons, their French allies and the powerful Iroquois Confederacy south of Lake Ontario, who had equally become engaged in the fur trade. The natives' growing dependence on European trade goods turned recurrent tribal warfare into a desperate contest for survival. By 1650 the Hurons had been fragmented and dispersed by Iroquois military strength, and the French on the St. Lawrence forced to a grim defensive. Over the next decade, New France strained for its own survival—until the French mother-state, rising to new heights in Europe, turned to restoring Canada. An efficient system of royal government, directly under crown officials, replaced company rule there in 1663. Large forces of regulars were sent out, who drove the Iroquois to peace by 1667. And New France surged with growth as a colony, thanks to the care and funds provided by the French state, now become Europe's leading power.

The work of development was well supervised by Jean Talon, as intendant under royal government, the colonial official mainly charged with internal affairs. Families of settlers were sent out by the Crown, selected marriageable young women, contracted labourers, equipment and livestock. Arriving immigrants were placed on great estates granted to seigneurs, the land-holding group who thus served as settlement agents. Talon's accompanying efforts to diversify farming, promote lumbering, shipbuilding, weaving, tanning and still more, met with varying success; but at least solid agricultural underpinnings were added to New France's continued reliance on the fur trade. Above all, settled population tripled between 1663 and 1673, from about 2,500 to over 7,500. Thenceforward the home country's finances and manpower were caught up in wars in Europe, and immigration to French Canada, no longer supported, sank to trickles. Nonetheless, the community grew from within to about 10,000 by 1680, and steadily thereafter. A French-speaking society had been securely entrenched in the St. Lawrence valley, not only in lines of sturdy farmhouses edging the central river, but in the prospering towns of Quebec and Montreal, that were markets for the rural areas as well as control points for the basic fur commerce.

Growth, moreover, went on in seacoast French Acadia, though it was more uncertain and restricted. In fact, Acadia had been in English hands for various periods between 1613 and 1667; and afterwards the fast-enlarging English colonies in New England down the seaboard continued to push their trading and fishing interests north into this marginal zone between two major empires. In spite of the stresses, however, a French Acadian community of some 800 had arisen by the 1680s: fishermen or farm families occupying the lush tidelands of the Bay of Fundy, and chiefly centred around Port Royal, Acadia's small capital and military base. In the meantime, English Newfoundland had probably come to hold around 1,100 permanent residents, greatly outnumbered each summer by the seasonal fishermen arriving from England. Hence both the St. Lawrence and Atlantic regions now contained limited but lasting cores of European settlement.

A strengthened New France vastly expanded its fur trade through the 1670s and 80s. Peace with the Iroquois had re-opened the routes west; the Huron-middleman structure had vanished; adventurers from the St. Lawrence thrust out over the Great Lakes basin to reach new fur supplies. They journeyed south of the Lakes and down the Mississippi, which the supremely adventurous La Salle followed to its mouth in 1682. They advanced west and north, claiming the Great Lakes country and the territory up to Hudson Bay. French forts appeared from Fort Frontenac (Kingston), where Lake Ontario meets the upper St. Lawrence, to Niagara and the Illinois country; from Michilimackinac at the head of Lake Michigan to Kaministiquia near the tip of Lake Superior. The expansionist drive, eagerly pushed by the governor general of New France, the Comte de Frontenac, gave the French a tenuous hold over inland America from the Gulf of Mexico to James Bay. Yet it also ran into growing troubles with English trade rivals, both to north and south.