When new settlers started to head westwards into the United States and into territory of the Native Americans often battles broke out. These battles are known together under one name, the American Indian Wars.

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The battles in the American Indian Wars are thought to have started with the Jamestown massacre in 1622. Soon other small conflicts regularly started, which almost always ended with the victory of the settlers. East of Mississippi more battles broke out after the Revolutionary War. These were not huge battles, with a few thousand solders maximum on each side, except the War of 1812, where over 10,000 Natives fought with the British Empire against the United States. The wars east of Mississippi ended in 1842 with the Second Seminole War, a six year lond war in Florida between the Seminole tribes in Florida and the United States. After the war, which ended with United States victory, the Seminole moved to a reservation in Central Florida.

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Most of the battles on the East Coast are not very famous battles and often forgotten when the American Indian Wars is mentioned. However the battles east side of the river are much better known.

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The conflicts in the west started in 1811 with the Battle of Woody Point, which rather astonishingly was a sea battle, which feature Tonquin, a United States registered merchant ship and two large war-canoes. The captain of Tonquin had insulted the chief of the Indian tribe Nootka, which resulted in an attack on the ship. 22 of the 23 men in Tonquin crew were killed and the ship was sunk by the only living member of the crew. 

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The wars in the west lasted much longer than the wars in the east. For example did the the Texas Indian War change belligerents four times. First Spanish Texas fought the Indians, then Mexico took over Spain's part, then the Republic of Texas, which 10 years later became a state in the United States. The half a century the war lasted, the Comanche fought four different countries, at separate times.

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​​​The most famous war has to be the Great Sioux War of 1876 or the Black Hills War. This is where three Indian tribes, Lakota
Cheyenne and Arapaho fought heroically against United States battle squad and three other tribes. The commanders of the Lakota tribe, Crazy Horse and Sitting Bull became very famous after the war, specially for the Battle of the Little Bighorn. This is the battle where the four battle chiefs of the Lakota, Cheyenne and Arapaho tribes, Sitting Bull, Crazy Horse, Chief Gall and Lame White Man, who died in the battle, led their side to the victory over the United States. This battle, which only featured around 2300 men, is by far the most famous Indian battle. United States defeated in the battle was so unexpected that it has become one of the favorite events for historians. At the end the United States did win the war, but the Natives who fought against them are remembered for their battle. ​

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The American Indian Wars didn't end until in 1924, when the Apache Wars ended and the Apaches became the last tribe to move into a reservation. At this time there were 302 years since the wars started. Minor battles however continued in Mexico until 1930.