The Werewolf Genocide was a campaign launched by the vampires to eradicate the werewolves. This campaign originated from the fact that a werewolf's bite is fatal to vampires. Very few werewolves escaped from this purge and the remaining ones formed packs to survive such as the pack formed by Jules, Brady and Mason Lockwood. The genocide happened a long time before modern times and the werewolves that survived were so few that even a majority of vampires believed them to be a mere legend.
Massacre of Ansel's pack
Ansel lived in the 10th Century, the leader of a pack of werewolves in the land that would one day become the town of Mystic Falls. A powerful chief, Ansel followed what are now known to the wolves as the 'old ways'. These include a more warrior-like culture for the members of the pack and embracing one's wolf form by killing a human during the 'Blood Moon'. The pack would also hold the life of its own as more sacred than anything.
At some point in the late 900s, a new family came to the New World: the Viking Mikael and his wife, Esther, a witch. They came with their friend, a powerful witch named Ayana, and their two children: Finn and Elijah. The death of their first child, Freya, from the plague led them to their exile from Europe. The new family quickly integrated themselves into the life of the village, with Ayana becoming the village healer. This peaceful coexistence would continue for several years to come.
The death of Freya had driven Esther and her husband apart. As Mikael continued to shun his wife, Esther begun to take an interest in the young werewolf leader of the village. She would later tell their son Niklaus that he was greatly admired by his pack and the others for his leadership. Esther quickly found herself falling in love with Ansel, feelings he reciprocated. They begun an affair, one which resulted in the birth of Niklaus.
Although she did not regret her decision or her love for Ansel, Esther knew that should Mikael learn of their affair that he would kill them all in his rage. Instead, she ended her relationship with Ansel and returned to Mikael so that he would believe that Niklaus was his son and not the son of another. Niklaus's birth renewed Mikael's hope of a family and Esther would later have three other children by him: Kol, Rebekah and Henrik.
However, Esther's love for Ansel remained strong for she apparently started working on a ring which would allow the wolves from no longer having to turn on the full moon. However, before she finished working on it, another death struck the Mikaelson family: Henrik was killed by the turned wolves the night he and Klaus went to see them turn, against the laws of the village. Another child's death led Mikael and Esther to try and protect their children through magic. Esther cast a spell which made her children into the first of the vampires. The bloodlust of this new species led them to slaughter half the village in their hunger.
When Niklaus made his first human kill, his werewolf side was triggered, making him the first hybrid. Mikael discovered that he was not his son and, in his rage, he slaughtered Ansel and half the village's werewolves before forcing Esther to suppress Niklaus's werewolf side. Ansel's death and the massacre of his pack was the first seed for the war that started between vampires and werewolves, a war that continues to the present day.
1st massacre of Guerrera Family: Papa Tunde
In 1919, two male members of the Guerrera family had a business meeting with Klaus and Elijah in New Orleans. Though a specific date was not given, it can be assumed by the illegal deal the men were all striking that the meeting was held at the start of or during the era of Prohibition.
Klaus called out the two members of the Guerrera family by referring to their crime family as a “brutish pack of thieves and killers,” and further stated, “that’s nothing compared to what [they] turn into on a full moon." Elijah attempted to defuse the situation, by first explaining to the two men that their werewolf bite would not kill an Original vampire, and by then reminding them that a war between the werewolves and Original vampires would not be financially profitable. Elijah proposed the following deal to the representatives of the Guerrera family: since Prohibition was soon going to become effective in the state of Louisiana, he and Klaus feared that the increased federal presence at the docks, which the Mikaelsons controlled, would result in their exposure to their father; to remedy this, Elijah and Klaus offered to allow the Guerreras to smuggle alcohol into the city through the ports, under the condition that the Guerreras publicly acted as the ones in charge of the port (though the Mikaelsons would secretly still be in control).
This deal was interrupted by Papa Tunde, who had a deal of his own that he wanted to make. Marcel, who recounted this story to Cami in the present day, later mentioned to Cami that Papa Tunde killed many members of the Guerrera pack when they refused to comply with his rule, along with many witches and humans who also opposed him. It was shown in a flashback that Papa Tunde had put the heads of the Guerrera wolves he killed on spikes to send a message to the rest of the community.
2nd massacre of Guerrera Family: Marcel Gerard
In 1925, the Guerrera Family engaged in a heated war with Marcel Gerard and his vampires. According to Marcel, the Guerreras were tough fighters, much tougher than the Crescents, and the vampires took out the Guerreras using guerrilla tactics over the course of several days. The war caused a death of about 100 werewolves. Marcel went on to believe that he had wiped out their entire bloodline, not knowing that baby Gabriel Guerrera had survived and was adopted by another family, who gave him the new name Gabriel Correa. Through two generation, Guerrera werewolves didn't trigger a curse, until Francesca Correa and her brothers took revenge on Marcel's Army.
- A Werewolf Genocide occurred in The Twilight Saga as well. The werewolves, known as the Children of the Moon, were also driven to near-extinction by vampires who saw them as a threat.
- Vanessa Monroe mentions that the werewolves are almost extinct, according to the legends in Bad Moon Rising. Katherine Pierce confirms her words when she has a conversation with Stefan in Memory Lane.
- Despite the fact that werewolves are supposedly almost extinct, they seem to have grown in numbers over the centuries. This is proved by the fact that Klaus has created multiple hybrids and given that the werewolf gene can lay dormant for generations. It's impossible to say for certain if they are as endangered as the show states.
- Rebekah committed Werewolf Genocide and added to the werewolf death toll in Crescent City.