Heptathlete Ashton Eaton bettered his world mark and further wins for high jumper Chaunte Lowe and 400 metres runner Sanya Ross-Richards took the U.S.'s gold medal tally to five.
While not garnering golds like the U.S, host nation Turkey had something to cheer with their first ever world indoor medals thanks to a second place for Kenyan-born Ilham Tanui Ozbilen in the men's 1,500 behind Morocco's Abdalaati Iguider and third for Asli Cakir Alptekin in the women's race, which was won by Genzebe Dibaba of Ethiopia.
Gatlin, who tested positive for testosterone in 2006, kept low out of the blocks and had edged clear of the field by the time he looked up to win the 60 metres title in 6.46.
"I'm just thankful. I wasn't trying to come back and do anything extraordinary, I just wanted to come back and be myself the way I left and I'm on the road to doing that," the quietly spoken Gatlin said.
"I think I can go out there and dominate and win the fans back," added the 2004 Olympic 100 metres champion.
Nesta Carter took silver with a time of 6.54 as once again, Jamaica failed in their bid to win a first men's 60 title at the championships and Britain's Dwain Chambers, champion two years ago in Doha, happily settled for third in 6.60.
"I knew it was going to be tough with those guys. But to get back on the podium again is a great feeling. It show's that the old boy's still got it in the old legs, the 33-year-old said.
Eaton's heptathlon world record was his third since breaking Dan O'Brien's 17-year-old mark of 6,476 in March 2010.
The American was in imperious form, He had a 165-point-lead after Friday's four events. With the gold medal in the bag by the fifth, the 60m hurdles, Eaton was free to concentrate on the world mark.
Needing to run two minutes 39.63 seconds or faster in the final discipline, the 1,000 metres, the 24-year-old shot off from the gun and crossed the line well clear of the field in 2:32.77.
"It feels good," Eaton said. "Coming into the competition, I knew I could break the world record. The competition was solid, I didn't have a bad event."
Both multi-event records have been broken at this world indoor championships. Nataliya Dobrynska of Ukraine became the first woman to go over 5,000 points in the pentathlon on Friday with a total of 5,013.
Australian Sally Pearson made her trip worthwhile with gold in the 60 hurdles in a world leading time of 7.73.
American-born Tiffany Porter, dubbed a 'Plastic Brit' by some sections of the British media after switching nationalities by virtue of dual citizenship, was second.
Yamile Aldama, another foreign-born Briton, gave the country their first gold of the championships winning the triple jump at the age of 39, 15 years after making her first appearance at the world indoors when she was competing for her native Cuba.
Lowe became the first American to win the women's high jump title, clearing 1.98 but the silver was a three-way split between Russian Anna Chicherova, Antonietta Di Martino if Italy and Sweden's Ebba Jungmark after they all jumped 1.95 with identical records.
Nery Brenes gave Costa Rica their maiden world indoors medal with a championship record of 45.11 in the 400 metres and Brazil's Mauro Da Silva won the men's long jump on countback from Henry Frayne of Australia after both athletes leaped out to 8.23 metres.
New Zealand's Olympic and world outdoor shot put champion Valerie Adams threw 20.54 metres to defeat arch rival Nadezhda Ostapchuk of Belarus and add the indoor title to her tally.
European champion Renaud Lavillenie of France won the men's pole vault.
Eaton started the second day 165 points ahead of Kasyanov and extended his lead by winning the 60 metres hurdles in 7.68 seconds, more than half a second quicker than the Ukrainian who was seventh in 8.39.
The American then cruised through the pole vault without a failure until 5.20 metres, long after his last remaining rival Lukyanenko had dropped out with a best of 5.00.
Eaton cleared 5.20 on his second attempt, doing a back somersault on the mat in celebration.
The record was never really in doubt as, cheered on by the near-capacity evening crowd, he pulled away from his fellow heptathletes over the five laps of the 1,000 metres.
"You do something the first time, you are like, 'Wow I did it'," said Eaton, perhaps the best runner of the modern-day multi-eventers. "It felt really good.
"Then you do it again and you are like, 'Yes I knew I could do it because I did it before'."
Eaton is now gunning for Czech Roman Sebrle's decathlon world record of 9,026 points.
"At this point, if all the stars are aligned perfectly, I think it could be possible," he said.