Process 1 onion with ¼ cup water in a food processor until pureed and the mixture resembles slush, about 30 seconds. Strain the mixture through a fine-mesh strainer into a liquid measuring cup, pressing on the solids with a rubber spatula or wooden spoon to obtain ½ cup juice. Some solids may seep through, that's okay. Discard remaining solids that remain in strainer.
In a medium bowl, whisk together the onion pulp, 1 cup ketchup, 5 Tablespoons molasses, 2 Tablespoons vinegar, 2 Tablespoons Worcestershire, 2 Tablespoons mustard, 1 ½ teaspoons liquid smoke, 1 teaspoon hot pepper sauce, and ½ teaspoon black pepper.
Heat 2 Tablespoons oil in a large nonreactive saucepan over medium heat until shimmering but not smoking. Add 1 garlic, 1 teaspoon chili powder, and ⅛-¼ teaspoon cayenne and cook until fragrant, about 30 seconds. Whisk in the ketchup mixture and bring to a boil; reduce the heat to medium-low and simmer gently, uncovered, until the flavors come together and the sauce is thickened, about 20 minutes. Cool the sauce to room temperature before using. The sauce may be refrigerated in an airtight container for up to one week or frozen for up to three months.