Place the watermelon chunks in a large freezer-safe plastic container and freeze them completely, 3 to 5 hours.
Add the frozen watermelon, tequila, and orange liqueur to a blender and blend until smooth. Divide among four glasses and serve with lime wedges.
Pineapple Jalapeño Margaritas: Use 4 cups frozen pineapple chunks and 1 or 2 seeded jalapenos in place of the watermelon.
Strawberry Margaritas: Use 4 cups frozen strawberries, 1 teaspoon balsamic vinegar (for sweetness and to cut the acid in the strawberries), and 1 teaspoon powdered sugar in place of the watermelon.
Virgin Margaritas: Swap the tequila and orange liqueur with ½ cup organic lemon-lime soda.