The correct answer is - climate change.
Even though throughout the geological past life on Earth have experienced extinctions caused by multiple different factors, like the extinction of the dinosaurs by a meteor crash, or the biggest extinction that the Earth have ever witnessed, the Permian extinction, caused by massive volcanic activity, still the dominant factor had been the climate change.
The climate change is the factor that was most often responsible for extinctions, and this is very simply because the animals are adapting to certain types of climate, and when the climate changes rapidly they are stuck in an environment in which they are not specialized to survive in, thus are dying out. A nice example is the end of the last ice age, when the temperatures grew significantly in a very short amount of time and the landscape changed dramatically, so most of the mega-fauna died out.