在歐洲人來到這裏之前，印第安人等北美洲的原住民生活在這片廣阔的土地上。相傳他們的祖先在大約一萬多年前經由西伯利亞跨過白令海峽來到北美洲，並且在這裏生存繁衍，他們沒有自己的文字，卻有着豐富的口頭文學。對於原住民的人口，歷史上的統計有很大出入，1492年（哥倫布第一次來到北美洲）的估測，北美印第安人總數大約有八百萬到一千萬人。隨着歐洲殖民者的深入，原住民的健康和領土受到嚴重威脅。由於歐洲人帶來的各種病菌，在150年內，原住民的人口銳減了90%；他們的村落被摧毀，原本用於畜牧或種植的土地被毀掉了。
前哥倫布時期（英語：Pre-Columbian）又稱印地安時期是指新大陸在明顯受到來自歐洲文化影響前的歷史時期。就字面上來理解，這段時期似乎指西班牙航海傢剋裏斯多福·哥倫布於1492年時第一次來到美洲大陸前的歷史，但實際上，“前哥倫布時期”通常還涵蓋到當地印地安文化在哥倫布登陸美洲大陸之後數十年，或幾世紀後的歷史，直到這些印地安文化顯著受到歐洲文化的影響及侵略。
“前哥倫布時期”這個詞常常在討論新大陸的印地安文明時提到，例如中部美洲諸文明──阿茲提剋帝國、馬雅文明，以及位於南美安地斯山脈的印加文明及莫切文化等等。
印第安人是對除愛斯基摩人外的所有美洲原住民的總稱。美洲土著居民中的絶大多數為印第安人，分佈於南北美洲各國，傳統將其劃歸蒙古人種美洲支係。印第安人所說的語言一般總稱為印第安語，或者稱為美洲原住民語言。印第安人的族群及其語言的係屬情況均十分復雜，至今沒有公認的分類。
印第安人在15世紀末之前本來並沒有統一的稱法。1492年意大利航海傢C·哥倫布航行至美洲時，誤以為所到之處為印度，因此將此地的土著居民稱作“印度人”（西班牙語：“indios”），後人雖然發現了錯誤，但是原有稱呼已經普及，所以英語和其他歐洲語言中稱印地安人為“西印度人”，在必要時為了區別，稱真正的印度人為“東印度人”。漢語翻譯時直接把“西印度人”這個單詞翻譯成“印第安人”或“印地安人”，免去了混淆的麻煩，到目前仍為最普及的用法。不過到了20世紀，許多美洲國傢印第安人的地位有了明顯改善，一些政府機構或民間組織開始對“印第安人”這一名稱進行“正名”，比如在加拿大往往被稱為更加政治正確的“第一民族”（英文：“First Nations”）等等。
屠殺與虐待
16世紀後來到美洲的歐洲殖民者帶給當地印第安人是毀滅性的災難。據統計，殖民時期，西班牙所屬的領地有1300萬印第安人被殺，巴西地區有大約1000萬被殺，美國西進運動中又有100萬左右印第安人被殺[來源請求]。目前大約有3000萬印第安人。大量印第安人被奴役甚至屠殺。拉丁美洲的男性印第安人基本上沒有純男性係列的後代，其混血後代麥士蒂索人大多為男性殖民者與當地女性的後代。而北美的情況更糟，印第安人被趕入印第安保留地，其在當地人口所占比例小於5%。在美國，印第安人僅占總人口的1%左右。
文化
印第安人經過兩萬多年的分化和發展，産生了許多不同的民族和語言。在歷史上印第安人曾建立過四個帝國，其中最重要的是北美洲的阿茲提剋帝國和南美洲的印加帝國。印第安人中的瑪雅人發明了瑪雅文字，對天文學的研究造詣也相當深入。印第安人培育出了玉米、馬鈴薯、辣椒、西紅柿、煙草、可可等作物。
然而，由於後來西方殖民者迫害、殺戮印第安人，毀滅印第安文化，致使現在殘存的古代文明材料已經不多，但目前的研究越來越引起考古界的關註，美洲國傢也開始下大力發掘古代印第安文化。
另外，印第安人曾被誤認為是紅種人，因為他們的皮膚經常是紅色的，後來纔知道這些紅色是由於印第安人傳統上習慣在面部塗紅顔料所給人的錯誤認識。
古代印第安人
在巴西亞馬遜地區的印地安人
* 瑪雅人
* 阿茲特剋人
* 印加人
和許多其他較小的部落。
The earliest known inhabitants of what is now the United States are thought to have arrived in Alaska by crossing the Bering land bridge, at least 14,000 – 30,000 years ago. Some of these groups migrated south and east, and over time spread throughout the Americas. These were the ancestors to modern Native Americans in the United States and Alaskan Native peoples, as well as all indigenous peoples of the Americas.
Many indigenous peoples were semi-nomadic tribes of hunter-gatherers; others were sedentary and agricultural civilizations. Many formed new tribes or confederations in response to European colonization. Well-known groups included the Huron, Apache Tribe, Cherokee, Sioux, Delaware, Algonquin, Choctaw, Mohegan, Iroquois (which included the Mohawk nation, Oneida tribe, Seneca nation, Cayuga nation, Onondaga and later the Tuscarora tribe) and Inuit. Though not as technologically advanced as the Mesoamerican civilizations further south, there were extensive pre-Columbian sedentary societies in what is now the US. The Iroquois had a politically advanced and unique social structure that was at the very least inspirational if not directly influential to the later development of the democratic United States government, a departure from the strong monarchies from which the Europeans came.
North America's Moundbuilder Culture
A Mississippian priest, with a ceremonial flint mace. Artist Herb Roe, based on a repousse copper plate.
Mound Builder is a general term referring to the original inhabitants who constructed various styles of earthen mounds for burial, residential and ceremonial purposes. These included Archaic, Woodland period (Adena and Hopewell cultures), and Mississippian period Pre-Columbian cultures dating from roughly 3000 BC to the 16th century AD, and living in the Great Lakes region, the Ohio River region, and the Mississippi River region.
Mound builder cultures can be divided into roughly three eras:
Archaic era
Poverty Point in what is now Louisiana is perhaps the most prominent example of early archaic mound builder construction (c. 2500 – 1000 BC). An even earlier example, Watson Brake, dates to approximately 3400 BC and coincides with the emergence of social complexity worldwide.
Woodland period
The Archaic period was followed by the Woodland period (c. 1000 BC). Some well-understood examples would be the Adena culture of Ohio and nearby states and the subsequent Hopewell culture known from Illinois to Ohio and renowned for their geometric earthworks. The Adena and Hopewell were not, however, the only mound building peoples during this time period. There were contemporaneous mound building cultures throughout the Eastern United States.
Mississippian culture
Around 900 – 1450 AD the Mississippian culture developed and spread through the Eastern United States, primarily along the river valleys. The location where the Mississippian culture is first clearly developed is located in Illinois, and is referred to today as Cahokia.