After labouring through her first match, surviving a match point in the second, American third seed Williams was finally put out of her misery in the third round when she was tossed out by rising Hungarian Agnes Szavay 6-0, 6-4.
But the tournament's first real shock could not match the commotion created by a 16-year-old grand slam debutante.
Fans scrambled for their earplugs at Roland Garros when the decibel level went up several notches before France's Aravane Rezai finally silenced Larcher de Brito 7-6, 6-2.
While Larcher de Brito deafened fans, top seeds Rafael Nadal and Dinara Safina made serene progress.
Four-times champion Nadal barely broke into a sweat as he overcame potential banana skin Lleyton Hewitt in a 6-1, 6-3, 6-1 hammering to extend his Paris record to 31-0.
The only drama came in the final point when Hewitt was unsure if Nadal had unleashed his seventh ace to win the match. The pockmark on the clay confirmed he had.
Russian Safina set up a last-16 date with Rezai by thundering past teenage compatriot Anastasia Pavlyuchenkova 6-2, 6-0 and holder Ana Ivanovic pulled off an equally emphatic 6-0, 6-2 drubbing of Czech Iveta Benesova.
Men's fourth seed Novak Djokovic wasted little time in finishing off Ukrainian qualifier Sergiy Stakhovsky 6-3, 6-4, 6-1 in their interrupted second round match.
Third seed Andy Murray reached the fourth round for the first time after Janko Tipsarevic retired hurt with the Briton leading 7-6, 6-3.
None of the big names could grab the spotlight from Larcher de Brito. So loud is her sonic boom, it lasts long after she has made contact with the ball and fans could have been forgiven for thinking Concorde was once again airborne and making an emergency landing on Philippe Chatrier Court.
Williams barely raised a groan as she was hopelessly outclassed by 29th seed Szavay who never lost belief during the 81-minute encounter.
In the only other upset, Romanian Victor Hanescu beat seventh seed Frenchman Gilles Simon 6-4, 6-4, 6-2.
Former champion Juan Carlos Ferrero also went out following a 6-4, 2-6, 6-4, 6-7, 6-3 defeat by Germany's Philipp Kohlschreiber in the second round.
Eighth seed Fernando Verdasco reached the fourth round for the third year running when he won the all-Spanish battle 6-2, 7-6, 7-6 against Nicolas Almagro.
Comeback queen Maria Sharapova overcame a miserable start to scrap into the fourth round with a 1-6, 6-3, 6-4 victory over Kazakh Yaroslava Shvedova.
Bhupathi-Knowles win
It was a mixed day for India as Leander Paes sailed into pre-quarterfinals of the men’s doubles but Sania Mirza crashed out of the women’s doubles event.
The 14th seeded Sania and Taipei’s Chia-Jung Chuang were knocked out 6-4, 6-7 (7-5), 3-6 by the unseeded Polish pair of Agnieszka and Urszula Radwanska. Third seeds Paes and Lukas Dlouhy staged a brilliant comeback to make their way into the last 16, defeating James Cerretani and Sergiy Stakhovsky 4-6, 6-3, 6-2.
Meanwhile, Mahesh Bhupathi and Mark Knowles began their campaign in the men’s doubles event with a comfortable 6-3, 6-2 win over Josselin Ouanna and Jo-Wilfried Tsonga.
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