By Agence France-Presse
Phelps clocked 52.38sec to finish ahead of longtime rival Ryan Lochte (53.11) and said he was just happy to be back after a six-month suspension by USA Swimming in the wake of his drunk-driving arrest in September.
"It does feel good to be back," said Phelps, who had last competed at the Pan Pacific Championships in August.
Fans in Mesa were less raucous than the crowds that cheered him last year when he returned from a nearly two-year retirement at the same meeting in suburban Phoenix.
But there was plenty of support for Phelps as he strode to the blocks in one of the new Xpresso racing suits that he helped manufacturer Aqua Sphere design.
Phelps said he'd been touched by the support he'd received, noting that fans in airports had wished him well, along with coaches and peers.
"It's amazing just to be in this environment again," said Phelps, whose arrest in Baltimore was followed by a stint in rehab and saw him axed from the US team for this year's World Championships in Kazan, Russia.
But Phelps says he has emerged with a better understanding of himself as a person and that his new perspective has renewed his passion for his sport.
Phelps's time on Thursday night didn't put him in the top 10 in the world this year in the 100m fly, an event he has won at three Olympics.
But he and coach Bob Bowman said the time, produced while Phelps is in hard training, was a good starting point from which to build as he eyes a fifth Olympics next year.
"First race back, it's OK," Phelps said. "Hopefully we'll be able to build and build.
"I think the more I race and feel confident with it, we can go out and control things," he added, noting that he'd only swum a handful of long course meets since returning to competition a year ago.
Phelps entered five events this week, with the 100m backstroke and 400m freestyle remaining for him on Friday and the 200m individual medley on Saturday.
The 400m free is a departure for him, but Phelps said he was looking forward to it as a chance to "see how much I can do, see how much I can hang."