In a blender, puree the watermelon and sugar until smooth. Pour the puree through a fine mesh strainer. Transfer the liquid to a pitcher and add the lime juice, tequila and 4 ounces of the Triple Sec. Stir to combine.
In a shallow dish, combine the kosher salt with the chili powder. In a second small plate, add the remaining 1-ounce of Triple Sec. Dip the rims of 4 margarita glasses in the Triple Sec, then coat them in the salt and chili mixture. Divide the margarita between the 4 glasses and garnish each with a lime wedge.