The book follows Isaac de Gimnebulin, a plump, middle-aged scientist of sorts who's been kicked out of the local university for conducting forbidden experiments and is dating a khepri woman (khepris have the bodies of humans but insect heads). You can probably tell this fantasy, and specifically in the sub-genre known as steampunk, where magic and industrial-era technology work side-by-side. The city where the story takes place, New Crobuzon, is a sprawling, polluted, Dickensian nightmare of factories, slums, and coal-belching railways.
When Yagharek, a garuda (a humanoid hunting bird) who lost its wings in a horrible way, comes to Isaac with a request for help in flying again, Isaac realizes that the problem could further his own research into crisis energy (sort of a link between magic and physics), and agrees to take Yagharek on as a client. Unfortunately, for his studies into flight, Isaac acquires a kind of caterpillar he's never seen before, one that seems to have psychic powers. When he finds the sort of stuff the caterpillar eats--a powerful hallucinogenic drug that's recently arrived in the city--it soon grows into a Slake Moth, a huge, dangerous, predatory insectoid creature that escapes and threatens all of New Crobuzon.
This is a good start to what happens, but this novel is so chockful--Isaac and his companions must travel through nearly all of the numerous neighborhoods of New Crobuzon throughout the book in their fight against the Slake Moth, encountering all the city's strange races and their varied customs, and every social stratum, from the poorest of the poor, to all the workers of its jobs, both wondrous and mundane, to the political elite, that it reads a little like a guidebook for the fictional metropolis.
In fact, my final impression after finishing reading, is that it's a love letter to urbanity, an ode to cities in all their grimy complexity, and how geography, industry, politics, crime, and recreation combine in endless combinations to make a distinctive urban environment. There's more than a little Victorian London in New Crobuzon, but it's more than that. When a woman at my son's fencing class was asking about the book, and I showed her the map of New Crobuzon at the beginning, her daughter exclaimed, "It looks like a brain!" And she was right--the map of the city looks like a brain, with its hundreds of connections and different functional areas. I think in the end, that might be exactly what China Mieville is getting at.