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Preheat the oven to 400 degrees F. Set out a 9-inch dep dish pie pan. Spray the pie pan with nonstick cooking spray.
Set a large sauté pan over medium heat. Add the ground beef, chopped onion, garlic, 1 teaspoon salt, and ½ teaspoon black pepper. Brown the ground beef, breaking it apart with a wooden spoon.
Once the beef is fully cooked, drain off most of the fat. Then mix in the pickle relish and mustard. Scoop the beef filling into the pie pan.
Fold the American cheese slices into triangle halves. Arrange the slices over the top of the ground beef. Then sprinkle the top with shredded cheddar.
In a small mixing bowl, whisk together the milk, Bisquick, and eggs. Pour evenly over the top of the cheese.
Bake for 25-30 minutes, until the top is golden and crusty. Cut and serve while warm.