Prepare the spice mix by combining smoked paprika, cayenne pepper, garlic powder, oregano, salt, and black pepper in a small bowl.
Pat the Mahi Mahi fillets dry with paper towels to ensure a good sear.
Rub the spice mixture generously over both sides of each fillet.
Heat the vegetable oil in a large cast-iron skillet over medium-high heat until shimmering.
Carefully place the fillets in the skillet, ensuring they do not overcrowd the pan.
Cook the Mahi Mahi for about 3-4 minutes on each side, or until the fish is cooked through and has a blackened crust.
Remove the fillets from the skillet and let them rest for a couple of minutes before serving.
Serve with lemon wedges for a bright and zesty complement to the blackened Mahi Mahi.