It is not certainly known how nearly he advanced to the mouth of that river on his passage from Gaspé Bay. But it is believed that he passed round the western point of Anticosti, subsequently named by him Isle de l'Assumption, and that he then turned to the east, leaving behind the entrance into the great river, which he then supposed to be an extensive bay, and, coasting along the shore of Labrador, came to the river Natachquoin, near Mount Joli, whence, as already stated, he passed eastward and northward to Blanc Sablon.

Cartier and his companions were favorably received on their return to France. The expectations of his employers had been to a certain extent realized, while the narrative of the voyage, and the prospects which this afforded of greater results in future, inspired such feelings of hope and confidence that there seems to have been no hesitation in furnishing means for the equipment of another expedition. The Indians who had been brought to France were instructed in the French language, and served also as specimens of the people inhabiting his majesty's western dominions. During the winter the necessary preparations were made.

On the May 19, 1535, Cartier took his departure from St. Malo on his second expedition. It was in every way better equipped than that of the preceding year, and consisted of three ships, manned by one hundred ten sailors. A number of gentlemen volunteers from France accompanied it. Cartier himself embarked on board the largest vessel, which was named La Grande Hermine, along with his two interpreters. Adverse winds lengthened the voyage, so that seven weeks were occupied in sailing to the Straits of Belle-Isle. Thence the squadron made for the Gulf of St. Lawrence, so named by Cartier in honor of the day upon which he entered it. Emboldened by the information derived from his Indian interpreters, he sailed up the great river, at first named the River of Canada, or of Hochelaga. The mouth of the Saguenay was passed on September 1st, and the island of Orleans reached on the 9th. To this he gave the name "Isle of Bacchus," on account of the abundance of grape-vines upon it.

On the 16th the ships arrived off the headland since known as Cape Diamond. Near to this, a small river, called by Cartier St. Croix, now the St. Charles, was observed flowing into the St. Lawrence, intercepting, at the confluence, a piece of lowland, which was the site of the Indian village Stadacona. Towering above this, on the left bank of the greater river, was Cape Diamond and the contiguous highland, which in after times became the site of the Upper Town of Quebec. A little way within the mouth of the St. Croix, Cartier selected stations suitable for mooring and laying up his vessels; for he seems, on his arrival at Stadacona, to have already decided upon wintering in the country. This design was favored, not only by the advanced period of the season, but also by the fact that the natives appeared to be friendly and in a position to supply his people abundantly with provisions. Many hundreds came off from the shore in bark canoes, bringing fish, maize, and fruit.

Aided by the two interpreters, the French endeavored at once to establish a friendly intercourse. A chief, Donacona, made an oration, and expressed his desire for amicable relations between his own people and their visitors. Cartier, on his part, tried to allay apprehension, and to obtain information respecting the country higher up the great river. Wishing also to impress upon the minds of the savages a conviction of the French power, he caused several pieces of artillery to be discharged in the presence of the chief and a number of his warriors. Fear and astonishment were occasioned by the sight of the fire and smoke, followed by sounds such as they had never heard before. Presents, consisting of trinkets, small crosses, beads, pieces of glass, and other trifles, were distributed among them.

Cartier allowed himself a rest of only three days at Stadacona, deeming it expedient to proceed at once up the river with an exploring party. For this purpose he manned his smallest ship, the Ermerillon, and two boats, and departed on the 19th of September, leaving the other ships safely moored at the mouth of the St. Charles. He had learned from the Indians that there was another town, called Hochelaga, situated about sixty leagues above. Cartier and his companions, the first European navigators of the St. Lawrence, and the earliest pioneers of civilization and Christianity in those regions, moved very slowly up the river. At the part since called Lake St. Peter the water seemed to become more and more shallow. The Ermerillon, was therefore left as well secured as possible, and the remainder of the passage made in the two boats. Frequent meetings, of a friendly nature, with Indians on the river bank, caused delays, so that they did not arrive at Hochelaga until October 2d.

As described by Cartier himself, this town consisted of about fifty large huts or cabins, which, for purposes of defence, were surrounded by wooden palisades. There were upward of twelve hundred inhabitants,[46] belonging to some Algonquin tribe.

At Hochelaga, as previously at Stadacona, the French were received by the natives in a friendly manner. Supplies of fish and maize were freely offered, and, in return, presents of beads, knives, small mirrors, and crucifixes were distributed. Entering into communication with them, Cartier sought information respecting the country higher up the river. From their imperfect intelligence it appears he learned the existence of several great lakes, and that beyond the largest and most remote of these there was another great river which flowed southward. They conducted him to the summit of a mountain behind the town, whence he surveyed the prospect of a wilderness stretching to the south and west as far as the eye could reach, and beautifully diversified by elevations of land and by water. Whatever credit Cartier attached to their vague statements about the geography of their country, he was certainly struck by the grandeur of the neighboring scenery as viewed from the eminence on which he stood. To this he gave the name of Mount Royal, whence the name of Montreal was conferred on the city which has grown up on the site of the ancient Indian town Hochelaga.

According to some accounts, Hochelaga was, even in those days, a place of importance, having subject to it eight or ten outlying settlements or villages.

Anxious to return to Stadacona, and probably placing little confidence in the friendly professions of the natives, Cartier remained at Hochelaga only two days, and commenced his passage down the river on October 4th. His wary mistrust of the Indian character was not groundless, for bands of savages followed along the banks and watched all the proceedings of his party. On one occasion he was attacked by them and narrowly escaped massacre.