Add the chicken, buttermilk, hot sauce, and 1 teaspoon of kosher salt to a large resealable bag. Toss and shake to coat the chicken. Let the chicken marinate in the refrigerator for at least 4 hours or overnight.
Heat 1½ inches of canola oil in a Dutch oven or large pot to 350°F.
In a wide bowl, combine the flour, remaining 1 teaspoon kosher salt, smoked paprika, ground cayenne pepper, and garlic powder. Remove the chicken from the buttermilk marinade and dip each piece in the flour mixture until well coated.
Fry 2 pieces of chicken at a time until golden brown and cooked through, about 4 minutes per side. Rest the cooked chicken on paper towels to cool.
Make the spicy mayo by combining mayonnaise, honey, hot sauce, and ground cayenne pepper in a small bowl.
Assemble sandwiches by spreading the open sides of the toasted brioche buns with sauce. Top the bottom bun with shredded lettuce, tomato, fried chicken, red onion, and the top bun.
