Final answer:
The worst defeat inflicted upon Native Americans was the American Revolutionary War and its aftermath, resulting in the destruction of Native American towns and loss of their lands and autonomy.
Step-by-step explanation:
The worst defeat inflicted upon Native Americans was the American Revolutionary War and its aftermath. While Native American leaders formed alliances with the British to protect their lands and interests, the Revolutionary armies destroyed Native American towns and crops. After the war, Native Americans were excluded from negotiations, resulting in significant loss of their lands and autonomy.
Additionally, the treatment of Native Americans by European colonizers led to their near destruction. Forced removals, enslavement, and the introduction of European diseases caused the death of millions of Native Americans. While the spread of diseases was unintentional, mistreatment and massacres worsened the situation.
Furthermore, conflicts with Native American tribes during westward expansion and the resettlement policies of the U.S. government led to the loss of Native American lands and way of life.