In a medium saucepan, combine ketchup, granulated sugar, brown sugar, vinegar, water, molasses, mustard, Worcestershire sauce, garlic powder, black pepper, salt, onion powder and liquid smoke. Bring to boiling; reduce heat. Simmer, uncovered, for 1 hour, stirring sauce often.
Remove from heat. Cool to room temperature. Cover and chill in the refrigerator for up to 2 weeks. Makes about 4 cups.