By 16th century, Portuguese and Spanish conquest and colonisation of America was under way. .
But European conquest was not the result of superior fire-power.
The most powerful weapon of the Spanish conquers was not the conventional military weapon but it was the germs of diseases such as smallpox that the conquerors carried on their persons.
Because of their isolation, American inhabitants did not have immunity to the diseases which came from Europe.
Smallpox proved a deadly killer. Once introduced it spread deep into the continent even before the Europeans could reach there. It killed and decimated reach people paving the way for conquest and colonisation.