Collision
The dinosaurs were wiped out when a big meteor or comet hit the Earth (K-T extinction event). It screwed up every ecosystem, both in land and in seas, produced mass extinctions of many types of animals and plants and changed the climate. However, smaller animals, like mammals and birds, indeed survived, but it was a very catastrophic event nevertheless.
If that happened nowadays, humans would surely survive thanks to technology and intelligence, but it would be a very hard struggle. This would cause havoc in agriculture, fishing, foresting and many other essential activities, which would lead to an economical crash and famine.
If something like K-T is not enough, maybe a higher dose like the P-Tr event is enough. Quoting wikipedia's article, "It is the Earth's most severe known extinction event, with up to 96% of all marine species and 70% of terrestrial vertebrate species becoming extinct." It triggered a sudden 8° C rise in temperature and an increase in CO2 levels by 2000 ppm. That was more than enough to mess up with Earth ecology everywhere. Nature took some millions of years to recovery from that. The cause of the P-Tr event is unclear, but a very large bollide hitting the Earth would do that.
Now, imagine a very large bollide hitting the Earth and obliterating a large area, say, half the size of Australia, part on sea and part on land. That area would then be turned into an open magma pit by exposing the mantle. It would also cause an earthquake and a tsunami as never seen before and would also release a lot of toxic gases from the exposed mantle, from vaporized crust and also those gases that were imprisoned in the crust. Also, a lot of seawater would be suddenly vaporized.
The atmosphere becomes severely dusty, and the blocked sunlight would be more than enough to create a winter that could trigger an ice age, if it were not the greenhouse gases preventing that. Since much less sunlight reach the surface, the life of many plants and animals both in land and in sea would be screwed. Also, since there is much more water vapour in the atmosphere, and then much more clouds, so there would be still less sunlight. From that, there would be horribly severe storms, hurricanes, floods and landslides. Also, the summers would be much more warmer and the winters much more colder. This would cause a severe death toll for land lifeforms and also for many aquatic forms. And oh, since the water in the rain will combine with the dust, the rain would be acidic and it could also acidify the seas.
The death toll would create a massive quantity of rotting organic matter (imagine something like the amazon forest suddenly dieing and rotting down all at once). A large part of that matter will be washed down to waters (seas, lakes and rivers), where it will tend to deplete water's oxygen in many places triggering anoxic events that will further extinguish many aquatic lifeforms. The rotting organic matter itself would release a lot of greenhouse gases and consume atmospheric oxygen. Needless to say, having less oxygen dissolved in waters and less oxygen in air would be no good for whatever ecology that are still resisting so far.
In the following years, as the dirty settles down, the greenhouse gases are still in the atmosphere and they will warm up the planet severely, further screwing up once again the already screwed up ecosystems. The removal of much of the previous forest cover would also create large desertic areas.
Very few forms of plants and animals are able survive that, but a few surely will. Among them, a few humans surely could do, but it would be no easy task.