Cartier set sail with three ships, "La Grande Hermine", "La Petite Hermine", and "L'Émerillon", along with Domagaya and Taignoagny acting as guides.

Cartier sailed up the St. Lawrence River, guided by Domagaya and Taignoagny. He reached the Iroquoian village of Stadacona (present-day Quebec City), where he was greeted by Chief Donnacona.

Against Donnacona's wishes, Cartier continued upriver to Hochelaga (present-day Montreal). He was impressed by the large village and the surrounding fertile land. He climbed Mount Royal, naming it after the King of France.

Cartier and his crew spent a harsh winter at Stadacona. They suffered greatly from scurvy, a disease caused by vitamin C deficiency. Many men died. The indigenous people shared a remedy made from the bark and leaves of a tree (likely white cedar), which helped cure the surviving crew members.

Despite Donnacona's initial hospitality, Cartier, showing a pattern of exploiting native trust, kidnapped Donnacona, Domagaya, Taignoagny, and several other Iroquoians to take them back to France. He promised to return them after a year.

Cartier returned to France, bringing the kidnapped Iroquoians and stories of the rich lands he had explored.