Answers (2)
What time period are you talking about? Which America and what region?
Before the Puritans arrived there was an epidemic along the eastern coast and roughly 90% of the tribes were wiped out. When the Spaniards arrived in Central America, diseases killed about 90% of some tribes that came into contact with the invaders. When the pioneers started moving west, many people were killed by various causes.
You are inquiring about 500 years of history. You can't expect to get that all in one snappy paragraph.
One of the biggest factors were the arriving settlers who were so selfish and hungry for land and money that they put poisons or disease strains onto quilts and giving them to the natives. A gift that kills. Also the cowboys who would scalp them or rape them, also burning down their teepees