Usually referred as "The Incident" by Frankenstein, it is an important event which resulted in the 820 years long slumber of Cadis Etrama Di Raizel. The Incident resulted in the disappearance of Rai from Lukedonia and Frankenstein's 820 years long desperate search for his Master.
The Incident paved the foundation for the many important events of future including the rise of traitor clan leaders and the downfall of Lukedonia, the rise of the supposed human organization "Union" and the so called disappearance of Werewolves.
The Incident is first mentioned by Frankenstein in Season 1 where he says that he hided himself from the Nobles as he believed that some of them might have been involved in the disappearance of his Master. This is further cleared in Season 3 in which we see a flashback of hundreds of years ago. Frankenstein informs Gejutel that he is leaving Lukedonia as he can't trust nobles. Frankenstein finds it suspicious that even after a long search by the clan leaders no clue regarding his master's disappearance was found. In another flashback we see Frankenstein leaving Lukedonia before informing Ragar Kertia that he can't trust anyone in Lukedonia as he felt an explosion when his Master disappeared but no traces were found by the nobles.
Frankenstein realizes that his suspicion was well founded when Rai reveals that the traitor clan leaders created a situation in which Rai had no choice but to use his powers. He states that he was in a similar situation as that of Seira's deceased father and Gejutel's dead son. (Seira's father and Gejutel's son went to human world to help humans but it was a trap formed by traitors who killed them).
In Chapter 280 we learn that traitors didn't attacked Rai directly as they would have taken serious injuries and thus noticed by Frankenstein or The Previous Lord. Frankenstein deduces that many were involved in the Incident other than the six traitor clan leaders.
In Chapter 311 Frankenstein reveals his theory: Muzaka, the former Lord of Werewolves, was responsible for putting his Master in his long slumber. Muzaka wanted to wipe out the human race 820 years ago but Rai stopped him and the resulting battle lead to their mutual destruction.
Muzaka's only daughter, Ashleen, was killed by humans which enraged him to wipe out the human race.
The details of how traitors were involved in this Incident are yet to be revealed in the manhwa. Noblesse: Beginning of Destruction explains the role of traitors in it.