Marinate the chicken (at least 1 hour, preferably overnight).
Place chicken pieces in a large bowl. Cover with buttermilk and hot sauce. Cover with plastic wrap and refrigerate.
Prepare seasoned flour (5 minutes).
In a large bowl, combine flour, salt, black pepper, paprika, garlic powder, onion powder, and cayenne.
Coat the chicken (10 minutes).
Remove chicken from buttermilk. Dip each piece of chicken into the seasoned flour, pressing the flour onto the surface to create a thick coating. Place coated chicken onto a baking sheet.
Heat the oil (10 minutes).
Fill a Dutch oven or deep pot halfway with oil. Heat over medium-high until it reaches 350°F (use a thermometer for accuracy).
Fry the chicken (12–15 minutes per batch).
Working in small batches, carefully lower chicken pieces into the hot oil with tongs. Fry until golden brown and cooked through (165°F internal temp). Dark meat usually takes 14–16 minutes; wings may take 8–10 minutes.
Drain & rest (5 minutes).
Remove fried chicken with a slotted spoon and place on a baking sheet lined with paper towels. Let rest 5 minutes before serving to allow juices to redistribute.