Karsus, one of the greatest archmages in Netheril attempted to usurp the godhood of Mystryl, the goddess of magic. His attempt failed, killing him and destroying Mystryl. Upon Mystryl's death, the Weave collapsed entirely, briefly causing all magic in Toril cease to function. WIth magic no longer functioning, the floating enclaves of Netheril began falling out of the sky. Most crashed into the ground, destroying them and killing all inhabitants.
Karsus's Folly
-339 DR, Year of Sundered Webs