The defeat continued Stosur's horror run at her home Grand Slam. The 2011 US Open champion has never ventured beyond the fourth round in 11 visits to Melbourne, including a first-round trip last year, reports Xinhua.
Stosur appeared to have the match in the bag only to twice falter while trying to serve it out and then dropping serve for a third consecutive time to hand the world No.40 victory after two hours and 42 minutes.
"Obviously it's a pretty hard one to take when you get yourself well and truly into a winning position." said Stosur. "Then all of a sudden you get to 5-2 and you lose five games straight."
The odds were stacked against Stosur when she dropped the opening set after 54 minutes.
Stosur had won only six grand slam matches from 37 tries after losing the first set and also lost to Zheng last week in Sydney.
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But the local star gritted her teeth to force a third set and raise hopes of a rare comeback win.
Former Wimbledon semi-finalist Zheng reeled off five straight games to snatch victory and set up a third-round clash Friday with No.18 seed Julia Goerges.