Stosur, the fifth seed in Sydney, never looked likely against her conqueror in the 2010 French Open final, giving up five breaks of serve against the world number 11 before going down 6-2 6-4 in one hour and 30 minutes.
Stosur's loss, coming on the back of a second-round defeat at the Brisbane International by Czech Iveta Benesova, must be of concern to the 27-year-old Queenslander, who broke through for her maiden grand slam success last September at Flushing Meadows.
In other results, third seed Victoria Azarenka of Belarus had no trouble disposing of Swiss qualifier Stefanie Voegele 6-2 6-1, and last year's Australian Open runner-up Li Na is safely into the second round after a 6-0 6-3 win over Russian Ekaterina Makarova.
Sixth seed Vera Zvonareva was a surprise casualty, going down 6-1 6-2 to to fellow Russian Svetlana Kuznetsova, but France's Marion Bartoli, the eighth seed, cruised past Slovenian Polona Hercog 6-3 6-3.
There was no love lost between the Radwanska sisters of Poland, with older sibling and seventh seed Agnieszka destroying qualifier Urszula 6-1 6-1, while Germany's Andrea Petkovic took care of Russian Anastasia Pavlyuchenkova 6-2 6-3.
Slovakian Dominika Cibulkova had to battle to make it past China's Peng Shuai, winning 6-2 4-6 6-4, and Cibulkova's compatriot Daniela Hantuchova swept aside Italian Roberta Vinci 7-5 6-2.
Chanelle Scheepers of South Africa dispatched Hungarian qualifier Melinda Czink 6-4 6-2, Romanian lucky loser Alexandra Dulgheru had few problems with Swede Sofia Arvidsson, winning 6-1 6-1, and Jelena Jankovic progressed when her opponent Julia Goerges retired hurt when trailing 6-1 3-1.