People always like to blather on and on about advanced tech and germs. That's a load of crap.

I think Cortez had less than 200 men under his command and they weren't wearing MJOLNIR armor from Halo with machine guns and rockets. They were just dudes with swords, firearms, and some steel armor. Throw enough Aztec Jaguars at them and they're gonna be zerg rushed into oblivion. Their firearms weren't even that great; fired one shot and then took aged to reload. There is a reason why bayonet charges continued well into the 19th century.

While germs did set off plagues of biblical proportions it wouldn't have much of an impact within the few short months it took Cortez to dismantle the Aztec Empire. Even then lots of people still survived and even in the midst of the Black Death in Europe wars were still being fought. Plague is deadly to people, but merely a hindrance to governments.

The real reason to the conquistadors success was politics. The Aztecs had subjugated their neighbors with fire and blood and treated their subjects with brutality. There was dissent and rebellion already fermenting within the Aztecs sphere of influence, if Cortez hadn't arrived a rebellion with native leaders would have risen up eventually. Imagine you're part of a subjugated tribe and this bad ass motherfucker in max level gear shows up, what do you do? Welll you're gonna help him overthrow your overlords of course! While they weren't invincible, the Spaniards equipment definitely made them deadlier and more durable than any single native warrior if you take skill and experience out of the equation. Throw in some horses for some cavalry charges and you have the equivalent of the Green Berets, Navy Seals, Marine Recon, Rangers, and Delta Force rolled into one. Put them at the helm of an army of disgruntled peasants and you have the perfect recipe for regime change. It wasn't 150 conquistadors against the might of the Aztec Empire, it was 150 conquistadors and 50,000 pissed off Maya, Olmec, and whatever other tribesmen lived in the area against the might of the Aztec Empire. Cortez was aided by allies that knew the land, knew the politics, and knew how the Aztecs fought.

The Spanish may as well have had the strategy guide along with cheat codes activated.

Pretty sure a similar thing happened with Pizarro and the Incas. These native American Empires weren't institutions, they were still relatively young and recently consolidated kingdoms when Europeans began to arrive. Discontent and rebellion was still rife within them.