Cuper's Cove, on the southwest shore of Conception Bay on Newfoundland's Avalon Peninsula was an early English settlement in the New World, and the third one after Harbour Grace, Newfoundland (1583) and Jamestown, Virginia (1607) to endure for longer than a year. It was established in 1610 by John Guy on behalf of Bristol's Society of Merchant Venturers, who had been given a charter by King James I of England to establish a colony on the island of Newfoundland. Most of the settlers left in the 1620s, but apparently a few stayed on and the site was continuously inhabited.

Tisquantum, more commonly known as Squanto, was a member of the Wampanoag Patuxet tribe best known for being an early liaison between the Native American population in Southern New England and the Mayflower Pilgrims who made their settlement at the site of Tisquantum's former summer village, now Plymouth, Massachusetts. The Patuxet tribe had lived on the western coast of Cape Cod Bay, but an epidemic infection wiped them out, likely brought by previous European explorers.