The 22-year-old, who swept to seven world titles two years ago, clocked a jaw-dropping 46.96 seconds in Gwangju to win swimming's blue riband event, with Olympic champion Kyle Chalmers taking silver.
"It hurt, it hurt really bad," said Dressel. "You don't get that magical feeling every night, you just got to shut the brain off and go," added the tattooed pin-up.
"I wanted to try to zone out the best I could, just let that instinct to training take over and put my head down, sacrifice the body and get my hand on the wall."
Dressel high-fived Australian rival Chalmers before perching himself on the lane rope as he milked the applause, raising a fist to flag-waving American fans.
Chalmers touched in 47.08 with Russia's Vladislav Grinev the best of the rest in 47.82.
Rio gold medallist Chalmers came into the world championships on fire, but Dressel exploded from the blocks and was half a body length in front at the turn.
Chalmers tried to fight back but Dressel had too much of a lead and the American romped home to bag his third gold medal of the week.
"I could see that Caeleb was a good body length off me on that dive," said the Australian.
"He took off and from then on it was really a chasing-down sort of a game. That the last 50 is his strength and I kind of saw him put his head down and take off a little bit."
Dressel could potentially surpass seven gold medals in 2017, which equalled countryman Michael Phelps's haul at the 2007 world championships in Melbourne.
Ever the perfectionist, swimming's new poster boy prefers to tweak and tinker, looking for ways to improve.
"Certainly there's some things I can clean up in that race," insisted Dressel.
"Coming off that second wall I was really sloppy on the breakout, and the first one to be honest.
"First three strokes coming off the first wall weren't the best thing either," he added. "There's things I've already thought about where I can get better."
Dressel will be hoping the magic returns for the 100m butterfly heats on Friday.
"It's so rare," he said of being in the zone. "I remember when you were like 12, 13 - you weren't even thinking about how you felt. You've got no muscle on the bones and you can just get up and go."