Lyles, who won bronze in the 100m, clocked 19.52sec for victory in what the American calls his "bread and butter" event. Lyles' teammate Kenny Bednarek took silver in 19.58sec, with Jamaican Bryan Levell claiming bronze in 19.64sec.
Olympic champion Letsile Tebogo of Botswana had to be happy with fourth, just a hundredth of a second off a podium place, while Anguilla-born Briton Zharnel Hughes was the only other sub-20 sprinter, fifth in 19.78sec.
Lyles, who ran the fastest ever semi-final performance in the history of any championships when he clocked 19.51sec on Thursday, was drawn in lane six, outside Olympic champion Letsile Tebogo and inside Levell and Bednarek.
Ever the showman, he was afforded a rapturous welcome as images were beamed up on the big screens by way of introduction at a packed-out National Stadium. He raised his arms high in the sky, holding the pose before releasing a bellowing roar as he flexed downwards. Bednarek, Levell and Tebogo were far more subdued.
There was no repeat of his over-hyped entry to the 200m final at last year's Paris Olympics though, when he was fined for his exuberant pogo stick-like display. Covid-stricken at the time, he went on to claim bronze as Tebogo won.
Lyles, not well known for his starts, immediately fell off Levell out of the blocks, but the American ran a masterful curve that saw him back in with a chance going into the home straight.
The American's top-end speed, coming into the final third of either the 100 or 200m, is unmatched on the circuit, and he made it count as he worked his way back from fourth place to fire through the line in first.
He roared as he came through the line, raising four fingers to acknowledge his four 200m titles and quickly seeking out his onlooking mother Keisha Caine Bishop in the stands.
