After qualifying for the final in seventh during a punishing schedule which meant Ledecky raced her semi-final 30 minutes after winning the 1,500m freestyle gold with a world record, the 18-year-old American touched first in one minute 55.16 seconds.
Ledecky's win, achieved from lane seven, added to her golds in the 400m freestyle on the opening night and the 1,500.
With all eight swimmers in with a chance of a medal at the final turn, Federica Pellegrini of Italy denied a United States one-two by claiming silver in 1:55.32 seconds. World champion Missy Franklin took bronze in 1:55.49.
Sun Yang of China dug deep, also from lane seven, to win his second gold, the men's 800m freestyle, after a thrilling battle with Italy's Gregorio Paltrinieri.
Briton Adam Peaty continued his fine form by adding the men's 50m breaststroke gold to his 100m breaststroke title, becoming the first swimmer to achieve the feat at a world championships.
Peaty won his third gold when he contributed to Britain's world-record time of 3:41.71 seconds in the mixed 4x100m medley relay, a new event.
Chad Le Clos of South Africa lost his men's 200m backstroke title to Hungary's Laszlo Cseh in a pulsating final.
Le Clos led for the first 100 metres but the Hungarian regained the advantage by the final turn. Although Le Clos made one final surge, Cseh did enough to post the year's world-leading time of 1:53.48 and hold off the Olympic champion by 0.20 seconds.
Cameron McEvoy of Australia clocked the fastest time in the world this year, 47.94 seconds, as he topped qualification for Thursday's men's 100m freestyle final.
His bid to succeed compatriot James Magnussen, the double champion who was forced to pull out of the championships with a shoulder injury, was given a major boost when Russia's Vladimir Morozov was disqualified in the following heat.
Morozov led throughout to record 48.12 seconds but was adjudged to have left the blocks too soon, a decision which silenced the near-capacity Kazan Arena. — Reuters
