The arrival of 'Equestria'.
If there was a moment where humanity as a whole was involved, it was this one. At first, it was a big mess: Intelligent equines that came with a huge continent-sized island, the misunderstandings that came with the first meetings, and among many, many other things... Equestria's magic.
The untouchable natural energy that gives the ponies their abilities with the weather, land, and magic itself... was lethal to humans.
And that's how the 'Conversion Bureau' became another important event in humanity's history. Perhaps the last one.
The only choice of survival for the humans was to transform into a pony, and while the barrier was expanding, the planet itself had some major changes.
Now, months after a complete conversion, Humankind is now Ponykind.
But...
Fate is always unpredictable.