Combine ice, lime juice, mezcal (or tequila), orange liqueur, agave and chile-lime seasoning in a cocktail shaker or jar with a tight-fitting lid. Shake for 10 seconds.
Rub lime wedge around the rim of a low-ball glass and dip in chile-lime seasoning, if desired. Fill the glass with ice and strain the cocktail into it.
Tip: Mezcal, tequila's smoky cousin, is made from fermented slow-roasted agave. It's traditionally enjoyed on its own, but we love the intensity it adds to margaritas.