Michael Phelps joined Ian Thorpe and Grant Hackett as the only swimmers to win six individual world titles with victory in the 200m individual medley.
Phelps had already won the 200m freestyle and a relay gold
The American held off Hungarian Laszlo Cseh to win his third gold medal of the championships in Montreal.
An hour earlier, Phelps had finished seventh as Italian Filippo Magnini won the 100m freestyle final in 48.12 seconds, the second fastest time ever.
Poland's Otylia Jedrzejczak broke her own world record in the 200m butterfly.
She overtook Australia's Jessicah Schipper in the final two strokes of a thrilling duel.
Both women went under the old world record mark, Jedrzejczak winning in 2:05.61, with Japan's Yuko Nakanishi a distant third.
Phelps went to Montreal aiming to win eight gold medals, but he was never a factor in the 100m free as Magnini held off South Africans Roland Schoeman and Ryk Neethling.
It made the Italian the second fastest man in history in the event after world record holder Pieter van den Hoogenband.
"I was really surprised Michael Phelps didn't get on the podium," said Magnini. "Along with the South Africans, he was the man I feared the most."
It was the second disappointing freestyle experiment for Phelps in Montreal, following his failure to reach the final of the 400m event.
He trailed for the first 100m of the individual medley after Cseh went through the butterfly and backstroke legs under world record pace.
But the American was in front when they switched from breaststroke to freestyle and pulled away to win in 1:56.68, with Cseh second in 1:57.61 and American Ryan Lochte third in 1:57.79.
The United States held off their Australian rivals to take gold in the women's 4x200m freestyle relay.
China took bronze ahead of the Great Britain quartet.
Australia did strike one gold when Giaan Rooney won the women's 50m backstroke final, with Gao Chang of China second and Germany's Antje Buschschulte third.