What decimated the native Americans were european germs. Whether through personal contact or "gifts" like infected clothes and blankets they had no natural defense.
Where do you think "War of the Worlds" got the basic plot.
Undisputedly true but only a part of the bigger picture. While it is true that native Americans had little to no resistance to new diseases such as smallpox, that didn’t remain a static fact. Early contact with Europeans was extremely dangerous for native Americans but successive generations were less vulnerable to these diseases.
Destruction of food sources and loss of territory was another factor. The loss of buffalo was damaging to plains Indians but not a concern for tribes that lived in other areas. However, the loss of any territory held by native Americans necessitated either relocation or assimilation.
The subduing of warring tribes was another factor. These native Americans needed to be conquered or sometimes eliminated to make way for settlers because there was no assimilation or coexistence possible.
And that’s just the native American aspect of “Winning” the West. There was also seizing control of lands held by other powers such as the British, Spanish, French and later Mexican rule.
There’s also the aspect of governing that vast territory. Settling territory involves taxing the occupants, enforcing laws, establishing communication, transportation and projecting military power.
“Winning” the west involved establishing sovereignty over a vast territory. Institutions such as the post office, courts, schools, churches, claims offices, and military bases were essential to those lands becoming part of the United States of America.