Keys recovered from a second-set wobble to see off former finalist Elena Rybakina 6-3 1-6 6-3 in a seesawing encounter on Margaret Court Arena on Monday.
A two-semi-finalist at Melbourne Park, most recently when she lost to Ash Barty in 2022, Keys is on another tear.
The world No.19 is riding a nine-match winning streak after taking the title at the season-opening Adelaide International, and again came out swinging against Rybakina.
Keys powered through the first set with some ferocious hitting before Rybakina, the sixth-seeded 2023 Open runner-up fought back to seemingly wrestle back the momentum.
Keys, though, was not to be denied, the American regrouping in the deciding set to advanced to a last-eight clash on Wednesday against the resurgent Elina Svitolina.
"It's hard to believe that it was 10 years ago that I made my first semi-final, but I'm really proud of myself today," Keys said.
"She raised her level in the second set and played some really great tennis.
"So to still be out here and playing some good tennis all these years later, I'm really happy."
Elina Svitolina scored her fourth-round win over Veronika Kudermetova. (James Ross/AAP PHOTOS)
Svitolina earlier continued her own inspired run to reach the Open quarter-finals for the first time in six years.
The one-time world No.3 turned doting tennis mum followed up her third-round elimination of fourth seed Jasmine Paolini with a straight-sets win over Veronika Kudermetova on Monday.
After falling behind 4-1 in the first set, Svitolina took full advantage of an unfortunate injury to Kudermetova to power past the wounded Russian 6-4 6-1 on Rod Laver Arena.
Now 30, Svitolina is playing some of her finest tennis and credits a happy family life with her veteran tennis-playing husband Gael Monfils and two-year-old daughter Skai for helping take her through to another Open quarter-final.
"I feel 2019 was a long time ago. So many things happen," she said.
"It was a lifetime ago. Having our daughter, Skai, and then surgery as well.
"So I'm really pleased with the performance throughout this tournament and just really, really enjoying this win today."
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Monfils plays American Ben Shelton later on Monday also striving to make the quarter-finals after ousting the men's world No.4 Taylor Fritz in the third round.
"I have time, a little bit, to do my recovery and then we will be all energy to watch his match and it's going to be an epic one, I'm sure," Svitolina said.
Going for broke, Kudermetova had raced out to her 4-1 lead in the opening set after breaking Svitolina twice in the first five games.
But the Russian quickly found herself 5-4 down after conceding four straight games, and then needing a medical timeout for an abdominal strain.
Svitolina showed great foot speed and deft touch to run down a Kudermetova drop shot and deliver a lovely cross-court winner to bring up three set points.
The 28th seed only needed two as Kudermetova fired a forehand long to hand Svitolina the set before taking a bathroom break to reset.
But nothing could stop Svitolina from progressing to a 12th grand slam quarter-final.
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