As an unfortunate twist of fate would have it, a convoy of flatbed trucks transporting nuclear waste from San Onofre was passing through Searchlight when the Great War broke out. Local police directed the drivers to temporarily park their vehicles in the town's fire station, but nobody had ever came back to retrieve them. There they sat in their extremely sturdy solid steel spent fuel flasks for over 200 years.
The New California Republic recently set up a sizable base here; this was a major obstacle for Caesar's Legion, due to its size and clear view of the surrounding desert. When it became obvious that a direct assault would not prove fruitful, Vulpes Inculta sent in some spies to learn more about the situation. After he learned about the radioactive waste being stored in the fire station, he ordered some unwitting legionaries to open the containers. Though the legionaries died almost instantly, the sacrifice produced a massive wave of death and ghoulification amongst NCR troops that effectively destroyed Camp Searchlight as a viable military base.
The area became highly radioactive. This action also resulted in the city having a green cloud hanging over it, which is most prominent during the night.
The aftermath of the Searchlight Sabotage appears in Fallout: New Vegas.