Melendez made his debut in the World Extreme Cagefighting and started off his career dominating his opponents, winning his first three career fights all by knockout due to punches before receiving an opportunity to fight for the first WEC Lightweight Championship against fan-favorite Olaf Alfonso at WEC 10. Melendez won the bout by TKO due to punches and became the first WEC Lightweight Champion. Two fights later, Melendez, still undefeated, made his debut in Japan's Shooto against Hiroyuki Takaya, which Melendez won by unanimous decision. He followed this up with two more TKO wins in Shooto to bring his record to 8-0 before making his Strikeforce debut against Harris Sarmiento, which Melendez won after his opponent tapped out due to punches received.