Merritt pulled away down the stretch Thursday night to win in 43.75 seconds - nearly a full second ahead of silver medalist Wariner, who finished in 44.74.
The third American in the final, David Neville, did a head-first dive across the finish line and wound up with the bronze in 44.80.
"I didn't have anything left," Wariner said. "I don't know what to say. I ran the best I could."
Wariner joins a long list of 2007 world champions from the United States who failed to win gold in Beijing.