O'Callaghan, McKeown in ominous Olympic form at Australian championships
In a high-calibre field featuring five of the 10 fastest performers in history, O'Callaghan touched first on the Gold Coast in 52.27 seconds.
Meg Harris (52.59), Tokyo Olympic champion Emma McKeon (53.09) and Shayna Jack (53.20) were all under the qualifying time needed to make Paris, while Cate Campbell and Brianna Throssell narrowly missed it.
It sets up a huge battle at the Australian Olympic trials in Brisbane in June with just two slots available.
"Pretty good time. I would have liked faster, but plenty more things I've got to improve," said O'Callaghan, who could target six gold medals in France.
Asked what she will be working on ahead of the Olympics, she replied: "Top secret."
All-conquering backstroke star McKeown swam the seventh-fastest 200m medley ever, touching in 2:06.99 to shatter an Australian record that had stood since 2009.
She is only the fifth woman ever to dip under 2:07 and just the second in the past eight years alongside Canadian sensation Summer McIntosh, who is set to be a key Olympic rival.
"I'm up for the challenge (of swimming the medley in Paris)," said McKeown, who owns the world records in all three backstroke disciplines.
"It'll be hard with the backstroke but I think I'm putting myself in a position to test myself as best I can."
In a race boasting the past three world champions, Elijah Winnington touched first in the men's 400m freestyle in a world-leading time this year of 3:41.41.
He edged Sam Short (3:41.64) and South Korea's Kim Woo-min (3:45.12), who swam on an invitation.
Zac Stubblety-Cook, the Tokyo Olympic 200m breaststroke gold medallist, took out the 100m title in 59.85, the only swimmer to crack one minute.
Ariarne Titmus clocked a competitive 8:17.80 to win the women's 800m freestyle less than two seconds ahead of Lani Pallister.
Titmus stunned Katie Ledecky to win the Tokyo Olympics 200 and 400m gold but finished second behind the American great in the 800m.
Ledecky has swum an 8:14.97 this year to lead the 2024 rankings.