One normal day in Ponyville a strange earth pony stumbles into town, muttering something about a disease and his family. When the Royal Guard goes out to investigate, they find a mare and filly long dead from a strange disease. They take the now three dead ponies back to Canterlot to investigate. Within two weeks almost every pony in Canterlot is dead, and ponies everywhere else are dying.
After a month, the few survivors gather in Ponyville and look for leaders. Two come forth. Princess Luna, who encourages a new refuge to be built in the mountains to the North. The other is a renewed-but also weak-Discord, who calls forth allies to help him rule Equestria with chaos.

A ponified version of The Stand by Steven King. It involves the mane six and many others.