Wilkerson was born in Tennessee to Roman Catholic parents in 1891. As a young man, he went to study medicine in Philadelphia, but had to abandon his studies in 1916 when his father died suddenly in New Jersey with debts to pay. Wilkerson agreed to manage a silent movie theater owned by a friend in Fort Lee, New Jersey. Wilkerson moved his wife and mother out west to Hollywood, California, where he started a new film industry trade paper, The Hollywood Reporter, in 1930. The clubs Wilkerson started in the 1930s on the Sunset Strip, a nightclub district in west Hollywood known for illegal backroom casinos, included Ciro's, the Vendome, Caf Trocadero, Sunset House, LaRue, and L'Aiglon. In 1940, he opened an illegal casino resort at Lake Arrowhead that was soon closed by authorities. A friend, Hollywood movie producer Joe Schenck, suggested he stop gambling in casinos and build one himself. Wilkerson named his project the Flamingo Club. But while working on it, with costs estimated at $1.2 million, Wilkerson needed to raise additional funds. In February 1946, he accepted an offer from an associate of East Coast organized crime chieftain Meyer Lansky to invest $1 million to complete construction. Wilkerson had known Bugsy Siegel in Hollywood since the 1930s. In June of 1947, Wilkerson was in Paris, France, and read the news that Siegel had been killed, on orders from his organized crime associates.