The youngest of thirteen children, Prudhomme was reared on a farm near Opelousas, the seat of St. Landry Parish, Louisiana. Members of his family had been active as cooks and in the restaurant business in and around Lafayette, Louisiana. In 1979, he and his late wife, Kay Hinrichs Prudhomme, opened K-Paul's Louisiana Kitchen in the French Quarter of New Orleans. In the early-1980s, the restaurant made the dish of blackened redfish famous. Once considered poor table fare, this fish gained popularity, due largely to the Cajun specialty dish that he created.
Prudhomme has been a key figure in taking Cajun cooking from a style little known outside of the Acadiana region of southwest Louisiana and propelling it to national fame. He is the creator of seasonings such as Meat Magic, Vegetable Magic, and Poultry Magic. He is sometimes credited with having invented the turducken, though this has not been verified.
On March 25th 2008, Prudhomme was grazed by a stray bullet while cooking at the TPC golf course in Avondale Louisiana. Prudhomme was attending The Zurich Classic where he was preparing fish. He felt something hit his arm and a .22 caliber bullet then fell from his sleeve. The bullet didn’t penetrate or cause any damage. Police said it could've been fired by a hunter in the rural area near the course. Police originally classified the incident as a shooting, but later reclassified it as a simple complaint. 1
Dom DeLuise is sometimes confused for Prudhomme. Both have a similar body shape and enjoy cooking. They both often wear "newsboy"-style cloth caps and beards.