Gamburyan began his career in 1999 at the age of 17. He won his first three fights, then lost a decision to future lightweight champion Sean Sherk in 2001. His cousin Karo Parisyan nicknamed him "Pitbull" for the tenacity he displayed in the fight. In 2007, Gamburyan appeared on the reality show The Ultimate Fighter 5, fighting on Jens Pulver's team. His nickname was changed to "Anvil" for his UFC career because "Pitbull" was already taken by other UFC fighters such as Andrei Arlovski. Manny defeated Noah Thomas by kimura lock in the preliminary round. In his next matchup, Gamburyan defeated Matt Wiman to advance to the semifinal round. In the semifinal round, Manny beat Joe Lauzon in a unanimous decision and advanced to the finale with Nathan Diaz. He was considered an underdog in each of his fights, in part due to his short stature. After the Lauzon fight, UFC president Dana White personally apologized to Gamburyan for doubting him. In the finale, Gamburyan controlled Diaz for the majority of the fight, but tapped out in the second round after dislocating his right shoulder on a successful takedown attempt. Despite losing the show, Gamburyan secured a UFC contract with his performance. He won his next two UFC fights, defeating Nate Mohr by ankle lock at UFC 79 and Jeff Cox by guillotine choke at UFC Fight Night 13. Gamburyan raised some controversy in the Cox fight by delivering a spinning leg kick after feigning the mutual tap of gloves that is often seen at the beginning of the match. The crowd in attendance reacted with heavy booing. He was KOed by Rob Emerson at UFC 87 in 12 seconds, one of the fastest knockouts in UFC history. Gamburyan frequently uses the System of a Down song "Toxicity" as his entrance music. Like Gamburyan, the members of System of a Down are of Armenian heritage.