Set your oven to 350°F (175°C) so it's fully heated by the time the meatloaf is ready to go in. Grease a 9x13-inch baking dish generously so nothing sticks once it's baked and bubbly. This small step saves a lot of cleanup frustration later.
In a small bowl, stir together the ketchup and barbecue sauce until fully combined. This glaze does double duty, since part of it goes into the meat mixture and the rest coats the top of the loaf. Set it aside while you build the meat base.
In a large bowl, combine the ground beef, crushed crackers, onion soup mix, eggs, and half a cup of the ketchup-barbecue mixture. Mix just until everything is evenly distributed, since overworking the meat can make the finished loaf dense and tough. Gentle handling here really does make a difference.
Press the meat mixture evenly into the greased baking dish so it forms a level layer. Spread the remaining ketchup-barbecue sauce across the top for that classic glazed finish. Slide it into the oven and bake for 30 minutes while you work on the mac and cheese.
While the meatloaf bakes, cook the macaroni noodles according to the package directions until just tender. Drain them well so excess water doesn't water down the cheese sauce later. Set the noodles aside for a few minutes to cool slightly.
In another bowl, whisk together the milk, condensed cheddar soup, salt, pepper, garlic powder, and onion powder until completely smooth. A good whisk here prevents any lumps of soup from surviving into the final bake. This sauce is what gives the mac and cheese its creamy backbone.
Stir the drained macaroni into the cheese sauce until every piece is coated. Fold in half of the shredded cheese blend, saving the rest for topping. This gives you a rich, cheesy mac and cheese ready to go straight onto the meatloaf.
Once the meatloaf has baked for 30 minutes, pull it from the oven and spread the mac and cheese mixture evenly over the top. Sprinkle the remaining shredded cheese over everything for that golden, bubbly finish. Return the dish to the oven for 17 to 20 minutes, until the top is melted and lightly browned.
Let the casserole sit for a few minutes once it comes out of the oven. This short rest helps the layers set so your slices hold together instead of falling apart. Then it's ready to cut and serve.