 Frenchman Samuel de Champlain had explored the area extensively in 1605 . He had specifically explored Plymouth Harbor , which he called " Port St. Louis , " and made an extensive and detailed map of it and the surrounding lands . Patuxet , the native village upon which the town of Plymouth was later built , was shown by Champlain as a thriving settlement . However , an epidemic wiped out up to 90 % of the Native Americans along the Massachusetts coast in 1617 – 1619 , including the Patuxet , before the arrival of the Mayflower . The epidemic has traditionally been thought to be smallpox , but a recent analysis has concluded that it may have been a lesser @-@ known disease called leptospirosis . The absence of any serious native opposition to settlement by the Pilgrims may have been a pivotal event to their success and to English colonization in the Americas . 
