Lochte swam the free leg of the 4x100 medley and guided the Americans to victory in a time of 3:21.03 ahead of Russia 3:22.86 and Australia 3:24.77.
The victory gave Lochte his sixth gold of this year's worlds and equalled his haul at the short-course event held in Dubai in 2010.
Earlier in the day Lochte won the men's 100 metres individual medley and swam second to Poland's Radoslaw Kawecki in the 200 metres backstroke.
Lochte notched up his second world record of the championships on Saturday when he beat Slovenian Peter Mankoc's 100m individual medley world record of 50.76 seconds with a time of 50.71s in his semi-final heat.
On Friday the 28-year-old shattered his own world record to win the 200 metres individual medley and then shocked the crowd by giving his medal away to a fan.
Japan's Kazuya Kaneda swam a championship record of one minute 51.01 seconds in the final of the men's 200 metres fly on Sunday, while Denmark's Rikke Pedersen won the women's 200 metres breaststroke final in a new championship record of 2:16.08. (Reporting By Mark Pangallo; editing by Toby Davis)