Nine-Tailed Demon Fox's Attack

The attack of the Nine-Tailed Demon Fox took place after the end of the Third Great Shinobi War, not long after the birth of Kushina Uzumaki and the Fourth Hokage's son, Naruto Uzumaki. Possibly, Madara Uchiha summoned and controlled it using Mangekyo Sharingan and ordered it to attack Konohagakure, although he claims it was a natural disaster.

Massacre
During the attack, the demon fox was destroying trees and several places. Iruka Umino's parents were one of the ones who were bravely fighting the demon leaving Iruka to see them. But he was taken for protection by two unknown Konoha ninjas. Several shinobi were trying there best to destroy the fox. Presumeably, Kushina could have been killed at this time.

Legacy of the Fourth Hokage
Konoha's population started to decrease. Until one ninja, known as the Fourth Hokage, with the cost of his life used the Dead Demon Consuming Seal and the Eight Trigrams Seal Technique to seal the demon into his newborn son, Naruto Uzumaki making him the host of the Nine-Tailed Demon Fox.