Puree watermelon in a blender. Wipe the rim of a margarita glass with a lime wedge; dip rim in salt.
In a cocktail shaker half-filled with ice, add tequila, orange liqueur, lime juice, jalapeno, and 2 ounces of the watermelon puree. Shake until very cold.
Strain into prepared glass. Garnish with watermelon wedge and jalapeno slice.
