Lyles came out on top of a thrilling race at the Stade de France on Sunday that ended in a photo-finish, to open his golden account.
The American was awarded victory over Jamaican Kishane Thompson by just five-thousandth of a second in the closest finish in modern Olympic history.
Lyles won three golds at last year's world championships in Budapest and the 27-year-old said he was eyeing a repeat in the French capital.
"I'm pretty confident, I can't lie," said Lyles.
He is seeking to emulate Usain Bolt, the last sprinter to achieve the treble.
The Jamaican legend did it at the 2016 Rio Games, having also done it four years previously in London.
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