Their team of Mollie O'Callaghan, Shayna Jack, McKeon and Meg Harris proved too hot to handle, touching in 3min 28.92sec ahead of the United States (3:30.20) and China (3:30.30).
Harris brought them home with a sizzling 51.94 after O'Callaghan led off to give them an immediate advantage.
McKeon, who was the star act in Tokyo and is at her last Olympics, won her sixth gold and 12th medal overall.
"Wow. I don't keep track of that kind of stuff ... it's an honour really," she told Australian media.
"To be part of this (4x100m relay team), it's extremely hard and this is a team of six with Bronte (Campbell) and Liv (Olivia Wunsch) -- we couldn't do it without this group of six.
"Everyone wants to be part of this team. I feel really honoured to be part of it."
It was the fourth successive Olympic gold Australia have won in the event, with the time second only to their own world record of 3:27.96 set last year.
They have held the world record since 2014, lowering it four times since then.
Winning gold was especially satisfying for Jack, who missed the Tokyo Olympics over a contested doping ban, which sent her "through hell".
"I already proved my redemption by coming here, so this is all fun and games for me, I'm just enjoying the experience," she said.
With the 2020 Games in her sights, her world came crashing down after testing positive for the muscle growth agent ligandrol in an out-of-competition test in June 2019.
She was banned for four years despite proclaiming her innocence, insisting the substance entered her system by contamination.
Ahead of Tokyo, the Lausanne-based Court of Arbitration for Sport concluded that "on the balance of probabilities" Jack "did not intentionally ingest ligandrol", but it was too late for her to make the team.
"It's a really special moment to stand on the podium with the other three girls, and represent the other girls from our heat swim," she said.
"I'm really proud of myself and how far I've come, but I definitely missed that opportunity in 2021."
