Bring a large pot of lightly salted water to a boil. Cook elbow macaroni in the boiling water, stirring occasionally until cooked through but firm to the bite, 8 minutes; drain.
Mix macaroni, 3/4 of the Cheddar cheese, asparagus, ham, onion, and mayonnaise in a bowl to coat pasta and vegetables in mayonnaise; season with salt and pepper. Spread the macaroni mixture into a 9x13-inch baking dish. Layer remaining Cheddar cheese over the macaroni mixture; top with bread crumbs.
Bake in the preheated oven until the breadcrumbs are golden brown, about 30 minutes.
