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Preheat the oven to 350ºF. Spray a 3 quart baking dish with nonstick cooking spray.
Bring a large pot of water to a boil. Salt generously, then add the pasta and cook until al dente. Drain and reserve.
While the pasta is cooking, place a large pot or pan over medium-high heat. Add the butter and melt. Once melted, add in the onions and cook until the onions are tender. Add the garlic and cook another 30 seconds.
Sprinkle the flour into the pan and whisk until there are no clumps. Cook for a minute or two, then slowly whisk in the milk. Cook the mixture until it is slightly thickened.
Working in 3 batches, whisk in 2 cups of the Mozzarella, making sure all of the cheese is melted in between additions. Add in the tomato sauce and then the Italian seasoning. Stir in the pepperoni, then stir in the reserved pasta.
Transfer the mixture to the prepared baking dish. Top with the remaining cheese.
Bake the pasta until the cheese is melted and bubbling, 15-20 minutes.