Supervolcano Eruptions
The majority of people are aware that Yellowstone Park is perched above a supervolcano. A significant eruption last occurred 664,000 years ago. It was 1.3 million years before that. Many believe the math indicates that another one is imminent. Mind you, there is no scientific proof for that proposition. But even if it takes a thousand years, it will probably happen once more.
The ash from the volcano's next eruption will travel thousands of miles. Several neighboring states would be entirely submerged. There are also still larger supervolcanoes in the world. The Toba supervolcano in Indonesia erupted 74,000 years ago, triggering a worldwide cold that lasted over ten years. It's thought that it almost exterminated the human race as we were developing. There wouldn't be anything that humans could do to stop one of these supervolcanoes from erupting again.