 On March 16 , 1621 , the first formal contact occurred with the Indians ( or Native Americans ) . A Native American named Samoset , originally from Pemaquid Point in modern Maine , walked boldly into the midst of the settlement and proclaimed , " Welcome , Englishmen ! " He had learned some English from interacting with English fishermen and trappers ( most probably from Bristol ) operating in the region . It was during this meeting that the Pilgrims learned how the previous residents of the Native American village of Patuxet had died of an epidemic thought to be smallpox . They also discovered that the supreme leader of the region was a Wampanoag Native American sachem ( chief ) by the name of Massasoit ; and they learned of the existence of Squanto ( also known by his full Massachusett name of Tisquantum ) , a Native American originally from Patuxet . Squanto had spent time in Europe and spoke English quite well . Samoset spent the night in Plymouth and agreed to arrange a meeting with some of Massasoit 's men . 
