Smallpox first arrived in the Americas in 1519 on the island of Santa Domingo, where it killed half of the indigenous population. The disease moved quickly to the Antilles islands and spread through the Mexican Mainland by 1520. From Mexico, the disease spread further and faster than the Spanish explorers themselves. For the next five years, smallpox killed most of the native population of Panama. By the time it successfully crossed the jungle into South America, there was nothing left to stop it from continuing south through the Andes to the entire continent. It was so strong that any person who received news of the Spaniards' arrival could also have received the deadly disease. Smallpox caused the biggest loss of life ever to occur in the New World.
The spread of disease had a lasting impact on the Americas as well. In the face of so much death, native people often believed that their ancestral gods had abandoned them, so many of them turned to the Christian religion of their conquerors. As it became harder to find a husband or wife, marriage patterns in North American tribes also changed. Some their unique culture was lost.
As many as 40 or 50 million people lived in the New World when Columbus landed, but many of them died within decades from disease. Disease also wiped out much of the population in the Caribbean islands, Central America, and Peru. Disease was like a weapon - a weapon the Conquistadors didn't even realize they had. Certainly, they would not have been as successful in their destruction of the Americas without it.