Julian Williams lost his belts as challenger Jeison Rosario caused an upset to become the unified junior middleweight champion.
Saturday's bout did not go according to plan for Williams (27-2-1), who was knocked out in the fifth round by Rosario in Philadelphia.
Rosario (20-1-1) destroyed Philadelphia native Williams in his homecoming – the American fighting in his hometown for the first time since 2011.
Dominican boxer Rosario hurt Williams with an uppercut in the fifth before a couple of right combos rattled the WBA (super), IBF and IBO holder.
Rosario then sent Williams to the canvas and while the champion got back to his feet, the underdog unloaded a flurry of punches again, prompting the referee to step in and stop the fight.
"I've got to keep crying because I'm so emotional in this moment," Rosario said.
Williams added: "I'm sorry I couldn't get the win but I'll be back. We'll see if we can get it real soon."