The 19th-seeded Russian had never beaten Clijsters, who is still in the early stages of her return from retirement, in their four previous encounters.
Petrova wasted little time in stamping her mark on the match, keeping Clijsters off balance with powerful ground strokes and a clinical service game that stunned the Hisense Arena crowd into silence.
The Belgian, who won the US Open last year and the Brisbane International title shortly before the Australian Open began, won just five points in the first set and committed 17 unforced errors.
If she hoped the break into the second set would give her the time she needed to settle and begin a fight back, the Russian had different ideas, winning the first game of the set to love and then giving up just two points on Clijsters' serve in the next.
Clijsters appeared to have found some of her touch again when she held a break point, but Petrova refused to allow her to capitalise.
The Belgian had been heading for a rare 6-0, 6-0 victory until the 10th game of the match when she finally held her serve.
Clijsters is, strangely enough, the last woman to record a 6-0, 6-0 whitewash at Melbourne Park against Russia's Vasilisa Bardina in the first round 2007.
Petrova broke serve again and while Clijsters was able to stave off two match points when the Russian was serving for victory, she was unable to stop her opponent's irrepressible momentum.
Meanwhile, Alona Bondarenko ended a long drought against Jelena Jankovic with a third-round 6-2, 6-3 upset win.
The victory on Hisense Arena was the first for Bondarenko against Jankovic in 10 meetings, the Ukrainian having only previously taken one set off the Serb in nine matches.
It was also the first time Bondarenko, who won the Hobart International title last week, had advanced to the fourth round of a grand slam.
Jankovic is the second highest women's seed to be knocked out of the tournament after fifth seed Elena Dementieva was beaten by Justine Henin on Wednesday.
Earlier, Justine Henin reached a special milestone at the Australian Open when she beat Russia's Alisa Kleybanova 3-6, 6-4, 6-2 in a third round encounter on Friday.
The victory was the Belgian's 500th, putting her in an elite club of tennis professionals and still firmly in the spotlight at the first grand slam of the year.
Juan Martin Del Potro, Andy Murray and Andy Roddick all won their round matches with relative ease and the trio were joined in the fourth round by John Isner, the 2.06 metre American, whose main weapon is not hard to guess.
He thumped 26 aces past Gael Monfils in his 6-1, 4-6, 7-6, 7-6 win over the Frenchman to lift his total for the championship to 81.
He plays Andy Murray in the next round after the Briton overcame a back scare and more problems with his serve to beat Florent Serra of France 7-5, 6-1, 6-4.
"I don't think my serve is an issue at all. Everyone is panicking about my serve," Murray said.
"I'm happy with how it's gone. It's got better in each match, like I thought it would," he added.
Henin would have reached her landmark a lot earlier if she had not decided to suddenly quit the sport in 2008 when she was the number one player in the world.
Then again, she might never have made it at all had Kim Clijsters not won last year's US Open, inspiring Henin to join her fellow Belgian in making a comeback.
Henin's win over Kleybanova was not her best performance at Melbourne Park this week but enough to thrust her into the fourth round against Yanina Wickmayer, another unseeded Belgian.
Henin would have to win another four matches to claim the title but the question is already being asked. Can she possibly win the Australian Open in her second event out of retirement just as Clijsters did in New York?
"It's a big challenge to come back and I think I love challenges. That's the way I am," Henin said.
"I need always to push myself and to push the limits back. I'm very proud of what I'm doing right now. I enjoy my game out there. That's the most important thing," she added.
Her next opponent could provide some of the answers. Wickmayer sealed her place in the fourth round with a 6-1, 6-7, 6-3 win against Italy's Sara Errani and will give Henin a stern test.
UNDER SUSPENSION
Wickmayer made the US Open semi-finals last year and is ranked 16 in the world but was overlooked for the seedings and forced to come through qualifying because she was under suspension when the registrations for the Australian Open closed.
Dinara Safina and Maria Kirilenko also won on Friday and will now play each other in an all-Russian fourth-round clash on Sunday. Like the Belgians, the Russians are on the march.
Safina defeated Britain's Elena Baltacha 6-1, 6-2 in less than an hour and is slipping through the draw almost unnoticed even though she made the final in Australia last year and is ranked number two in the world.
"I managed to dictate from the first point of the match," she said. "I think everything was going right."
Kirilenko matched her best performance at a grand slam when she defeated Italy's Roberta Vinci 7-5, 7-6, showing that her first round win over Maria Sharapova was no fluke.
Roddick recovered from a set down to defeat Spain's Feliciano Lopez 6-7, 6-4, 6-4, 7-6. The American will next play Fernando Gonzalez of Chile after the 2007 Australian Open runner-up outlasted Evgeny Korolev 6-7, 6-3, 1-6, 6-3, 6-4.
Argentine Del Potro booked his place in the fourth round with a 6-3, 0-6, 6-4, 7-5 win over Germany's Florian Mayer.
Henin knocks Dementieva out
Sharapova knocked out of Australian Open
Henin to take up Sydney wildcard
Sharapova loses to Bondarenko
Spotted: Kim Clijsters in Cincinnati