Phelps led at every turn, and he really turned it on at the end to win in 1 minute, 54.84 seconds -- nine-hundredths ahead of the runner-up and the fastest time in the world this year.
"It feels good to be back on that side, but I'm sure that's not going to be the end of us going back and forth," Phelps said. "I'm just happy to be able to have a good race like that, kind of fold it all together."
For Phelps, it was an emphatic message on his 27th birthday that he intends to turn his last Olympics into another major medal haul. For Lochte, it was a gutsy performance coming just half an hour after he won the 200 backstroke.
"The best thing about swimming is racing and stepping up against the world's best," Lochte said before he returned for his third race of the night, the semifinals of the 100 butterfly.
Lochte finished third in his heat and set up one last race with Phelps on Sunday.
Phelps, the two-time defending Olympic champion in the 100 fly, advanced to the final with the another fastest time of 2012, powering away to win his heat in 51.35. Lochte tied for the sixth-fastest time in the semifinals (52.47), but this isn't one of his specialties. He'd need to pull a big upset to earn another Olympic event.
Lochte seemed to have Phelps' number when he beat him twice at last year's world championships, then kept the dominance going with a convincing win on the first night of the trials in the 400 individual medley.
But Phelps edged Lochte in the 200 freestyle, and now he's got two wins in a row against the only swimmer who seems capable of preventing him from making another serious run at eight gold medals in London.
"I'm sure there's going to be some more races like that over the next few weeks," Phelps said. "Ryan swam three great races tonight. That's a tough triple."
In other events on the sixth night of the trials, Jessica Hardy made up for the disappointment of missing out on the Beijing Games because of a failed drug test, winning the 100 freestyle.
Seventeen-year-old Missy Franklin moved a step closer to having a seven-event program in London, finishing second behind Hardy in 54.15, while 11-time Olympic medalist Natalie Coughlin missed out on her last realistic chance at an individual Olympic race.
"That was all my heart in that race right there," said Hardy, who won with a time of 53.96.
Coughlin finished sixth, the last spot that can earn a possible berth on the 400 freestyle relay. But, at best, she would probably only get a morning swim at these games, a far cry from the six medals she won in China.
Franklin also led the semifinals of the women's 200 backstroke, posting a time of 2:07.91. If she can finish strongly on Sunday, she'll have four individual events and all three relays on her Olympic agenda.
Rebecca Soni locked up a second individual race in London, cruising to an easy win in the 200 breaststroke. She was slow off the blocks and made the first turn in fourth, but there was never any real doubt about this one. Soni surged to the lead on the second lap and steadily pulled away, winning with the fastest time in the world this year, 2: 21.13.
Micah Lawrence is heading to the Olympics for the first time, taking second place in 2:23.03. But 30-year-old Amanda Beard missed out on making a fifth Olympic team, fading to sixth (2:26.42).
Lochte got started on his busy night by winning the 200 back. The 27-year-old was sixth at the first turn, but quickly moved toward the front and took the lead for good with a brilliant flip turn off the final wall. Pulling away, he won with a time of 1:54.54, second-fastest in the world this year behind Japan's Ryosuke Irie.
Tyler Clary took the second spot in 1:54.88, giving him two individual races at the Olympics. He has bounced back from the disappointment of finishing third behind Lochte and Phelps in the 400 IM.
Phelps and Lochte are both assured of at least four individual events in London, and it would take a major upset for Phelps to miss out on a spot in the 100 fly.
At the start of the evening, Anthony Ervin was the top qualifier in the 50 freestyle semifinals with a time of 21.74. Nathan Adrian and Cullen Jones, who went 1-2 in the 100 free the previous night, also advanced to the Sunday final.