Seizing the race by the throat, Ledecky was more than two seconds under the pace of the world record of 3:58.37 she set at the Pan Pacific Championships in Australia in 2014.
She remained under world record pace through 350 metres before settling for the third-fastest time in history.
"I could tell I was tightening up a little bit, but just knowing I had to get my hand to the wall pushed me through that," Ledecky said, admitting that she had trouble sleeping in anticipation of her first race of the trials despite her dominance of the past two years.
"It was a little hot going out," Ledecky's coach Bruce Gemmell conceded. "Sometimes we forget she's a 19-year-old girl. She gets excited."
It was the first step toward what could be an historic Rio campaign. Ledecky, who exploded on the international scene with an 800m free triumph in London four years ago, is entered in the trials in every freestyle event from 50m through 800m.
Leah Smith, a relay gold medalist at last year's world championships, clung to Ledecky's heels all the way, slicing nearly three seconds off her personal best to finish second in 4:00.65.
That makes her the fourth-fastest performer ever and promises a formidable US one-two punch in Rio – a fact that wasn't lost on Ledecky as she celebrated with her rival.
Kelsi Worrell earned her ticket to Brazil with a 100m butterfly victory in a sizzling 56.48sec.
That made her second-fastest in the world this year behind Sweden's Sarah Sjostrom.
Worrell, who won gold at the Pan American Games last year in her first international meeting, powered past 2012 Olympic gold medalist Dana Vollmer on the second lap, but Vollmer locked up second place and a chance to repeat in Rio in 57.21.
The 28-year-old Vollmer, who took time off after London to give birth to her son Arlen, now 15 months old, exchanged a long hug with her 21-year-old rival across the lane ropes at the finish.
"I've looked up to her so much," Worrell said of Vollmer. "She has a lot of wisdom and I'm hoping that she can pass some of that along to me this summer."
Kevin Cordes won the men's 100m breaststroke. Although his time of 59.18 didn't match his semifinal showing of 58.94, it was enough to hold off a charging Cody Miller by eight one-hundredths of a second.
"I knew it was going to be a race," said Cordes, who hadn't broken a minute in the event before Sunday, and lived through trials heartbreak four years ago, when a third-place finish left him out of the running for London.
"Definitely carried that for four years," he said. "I'm happy this time it's a little bit different."
