Something mundane made much worse.
Also, a disaster doesn't need to be quick.
A new ore has been found in the mountains. The metal has been extracted. It's very hard and dense. Nobody's sure what to do with it yet, as lead is much cheaper if you want density and its hardness makes ifit difficult to work. However, one researcher happens to put a piece down next to an inactive lantern and the treated fabric used to make the lantern brighter gives off a pale glow near the metal.
Now, there's an interesting property! A sheet of the new metal covered with lantern fabric makes for a dim, yet permanent light source. Too dim to read by, but usable as a sign that's visible at night. The idea catches on and work begins on refining the metal commercially to make signs. Soon an enterprising merchant gets the idea of making paint from the powdered metal and painting the sign on the back of the lantern fabric as a way to cut costs. The number of glowing signs in the city explodes.
Some minor problems are noticed. The metal is poisonous, impacting the health of the miners for the ore and the sign painters, but so is mercury or lead, and as most people aren't affected, it's ignored. Even when some sign-painting shops catch fire and their paint goes up in flames scattering the powdered metal around the city, it's hardly noticed except by a slight addition of glow in the areas of signs that were never painted. Then some bright spark gets the idea to use the spirits to increase the brightness of the signs.
It works. Really well. Even the background glow from the dust scattered by the fires is brightened. Then things take a turn for the worse. People who spend a lot of time near the brightened signs start getting sick. Worse, some of the more enthusiastic workers who try to brighten signs end up starting fires, resulting in ashes containing the powdered metal getting tracked around. Now people who weren't spending time near the brighter signs are getting sick.
A few researchers suspect the brightened signs, or their remains, to be the culprit responsible for the sickness in the city, but even that underestimates the problem. Brightening the sign also made any of the metal's dust that had settled near it beforehand as bad as the stuff in the sign itself, increasing the amount of dangerous contamination to be scattered in the event of a building going up in flames or collapsing, or even just people walking through dust near the sign.
The craze for brighter signs continues and more people get sick. Eventually a few people end up dying. That snaps people out of their euphoria about the signs and into panic about the sickness sweeping their city. Many leave, planning on coming back when the sickness has gone. Those who were sick and leave start to recover after a while away from the contamination. Those who were healthy and enter start to get sick. More and more people realise there's something there making them sick and leave, eventually evacuating the city. All the people leaving with contaminated dust on them end up depositing it along the roads out of the city, poisoning the land nearby and making it less productive.
Years later, the city is abandoned and the land near the roads out of it still has plants that grow stunted compared to those further away due to the contamination in the soil. Every now and then someone goes into the city to see if things have improved, but always end up coming out again after a few weeks to a couple of months once they start getting sick. It takes longer than it used to, but it still happens.