Werewolf curse that infects certain parts of the population and causes people to turn into werewolves whenever they happen to be outside at night. Society slowly devolves and exiles the infected, but the infected fight back at night when the uninfected are most scared and vulnerable. The fighting rages on for years until nobody is left.
Humanity evolves at the same time to overcome natural death and disease. There’s massive overpopulation and food shortages across the globe. Areas are overcrowded and nobody is dying. In order to thin out the population and preserve humanity, death squads are assembled to clear out entire areas and many welcome death, but many still fight to live. Society lasts for ages until the Earth is eventually engulfed by the Sun.
The Earth literally just starts tearing itself to pieces.
The Earth somehow is thrown way out of orbit and is on a collision course with a previously undiscovered planet that is full of sentient life, and said planet will be destroyed if our planet collies with theirs. To ensure their safety, they decide to blow our planet up.
All water has somehow been poisoned, no filtration system can clean it.
Every non-human creature on Earth just disappears. Humanity truly owns the planet but cannot exist for long. Many turn to cannibalism.