Hong Kong's Haughey, the 100m free silver medallist at the Tokyo Olympics and at the World Championships this year, powered to the win over Americans Torri Huske and Abbey Weitzeil, Huske finishing in 53.17 and Weitzeil in 53.53.
The victory at the meet in Greensboro, North Carolina, followed Haughey's two triumphs on Friday, when she beat Ledecky in the 200m free and returned less than half an hour later to upset Tokyo Olympic gold medallist Lydia Jacoby in the 100m breaststroke.
Ledecky, who had also settled for second in the 400m free behind Canadian teenager Summer McIntosh, closed with a characteristically dominant 1,500m win in 15min 46.38sec.
The seven-time Olympic champion, who eased to victory in the 800m free on Wednesday, was almost 25 seconds faster than runner-up Paige Madden.
Matt King won the men's 100m freestyle in 48.30sec with Ryan Held second in 48.36.
Caeleb Dressel, whose five Olympic gold medals in Tokyo in 2021 included the 100m free, was second behind Josh Liendo in the "B" final as he continues a comeback aimed at next year's Paris Olympics.
In other events on the final day of the meet American Regan Smith won the women's 200m backstroke in 2:04.27, with Claire Curzan second in 2:06.39 and McIntosh, who rarely races the event, third in 2:06.81.
Hungarian world champion Hubert Kos won the men's 200m back in 1:55.95.
Kate Douglass won the women's 200m breaststroke in a meet record of 2:21.87 ahead of US rival Lilly King (2:23.98) and Matthew Fallon won the men's 200m breaststroke in 2:09.49.
