
Mezcal is a Mexican agave spirit, made from dozens of agave species, far more than tequila’s single blue agave, under its own denomination of origin. In the traditional styles its signature is smoke: the agave hearts are roasted in earth-and-stone pits before fermenting and distilling, and that fire is what you taste.
Smoke is the whole reason it is in the recipe, and no other agave spirit has it: the smoke comes from roasting the agave in an earth pit, a step no other category shares. As a base it cannot be replaced; as a small accent it can, and the drink simply stops being smoky.
Blue agave only, and no roasting over fire. In a smoky Margarita or a Penicillin the smoke simply disappears and nothing in the build brings it back.
"Mezcal is smoky tequila"
They are cousins, not versions of one another: tequila is blue agave alone, mezcal draws on dozens of agaves under its own denomination, and the smoke is only the most audible of the differences.

Italian Mezcal Margarita
Tequila reposado

Mezcal Margarita
Mezcal

Naked & Famous
Mezcal, Herbal liqueur (e.g., Yellow Chartreuse), Aperitivo

Oaxaca Old Fashioned
Tequila reposado, Mezcal

Mezcal Martinez
Mezcal

Mezcal Negroni
Mezcal, Red bitter, Rosso vermouth

Smoky Tommy's Margarita
Tequila blanco

Mezcal Pornstar Martini
Dry sparkling wine, Mezcal

White Mezcal Negroni
Mezcal

Garden Sour
Mezcal, Tequila blanco, Rhubarb liqueur

Mezcal Mule
Mezcal

Pura Vida
Mezcal

Snowbird
Mezcal

Crimes Of Passion
Tequila reposado

Devil Smoked Margarita
Mezcal

Gun Metal Blue
Mezcal

Mosquito
Mezcal, Red bitter

Spaghetti Western
Tequila reposado

Tuxedo Affumicato
Mezcal

1910 Cocktail
Mezcal, Cognac, Punt e Mes

Kummel Ye Faithful
Mezcal

Snake Eyes
Mezcal

Tia Mia
Caribbean aged rum, Mezcal

Tommi’s Cocktail
Mezcal